May measurement month 2018 : A pragmatic global screening campaign to raise awareness of blood pressure by the international society of hypertension
- Beaney, Thomas, Burrell, Louise, Castillo, Rafael, Charchar, Fadi, Cro, Suzie, Damasceno, Albertino, Kruger, Ruan, Nilsson, Peter, Prabhakaran, Dorairaj, Ramirez, Agustin, Schlaich, Markus, Schutte, Aletta, Tomaszewski, Maciej, Touyz, Rhian, Wang, Ji-Guang, Weber, Michael, Poulter, Neil
- Authors: Beaney, Thomas , Burrell, Louise , Castillo, Rafael , Charchar, Fadi , Cro, Suzie , Damasceno, Albertino , Kruger, Ruan , Nilsson, Peter , Prabhakaran, Dorairaj , Ramirez, Agustin , Schlaich, Markus , Schutte, Aletta , Tomaszewski, Maciej , Touyz, Rhian , Wang, Ji-Guang , Weber, Michael , Poulter, Neil
- Date: 2019
- Type: Text , Journal article , Review
- Relation: European Heart Journal Vol. 40, no. 25 (2019), p. 2006-2017
- Full Text:
- Reviewed:
- Description: Aims: Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results: Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion: May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk.
- Authors: Beaney, Thomas , Burrell, Louise , Castillo, Rafael , Charchar, Fadi , Cro, Suzie , Damasceno, Albertino , Kruger, Ruan , Nilsson, Peter , Prabhakaran, Dorairaj , Ramirez, Agustin , Schlaich, Markus , Schutte, Aletta , Tomaszewski, Maciej , Touyz, Rhian , Wang, Ji-Guang , Weber, Michael , Poulter, Neil
- Date: 2019
- Type: Text , Journal article , Review
- Relation: European Heart Journal Vol. 40, no. 25 (2019), p. 2006-2017
- Full Text:
- Reviewed:
- Description: Aims: Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results: Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion: May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk.
May measurement month 2019 the global blood pressure screening campaign of the International Society of Hypertension
- Beaney, Thomas, Schutte, Aletta, Stergiou, George, Borghi, Claudio, Burger, Dylan, Charchar, Fadi, Cro, Suzie, Diaz, Alejandro, Damasceno, Albertino, Espeche, Walter, Jose, Arun, Khan, Nadia, Kokubo, Yoshihiro, Maheshwari, Anuj, Marin, Marcos, More, Arun, Neupane, Dinesh, Nilsson, Peter, Patil, Mansi, Prabhakaran, Dorairaj, Ramirez, Agustin, Rodriguez, Pablo, Schlaich, Markus, Steckelings, Ulrike, Tomaszewski, Maciej, Unger, Thomas, Wainford, Richard, Wang, Jiguang, Williams, Bryan, Poulter, Neil, M. M. M. Investigators
- Authors: Beaney, Thomas , Schutte, Aletta , Stergiou, George , Borghi, Claudio , Burger, Dylan , Charchar, Fadi , Cro, Suzie , Diaz, Alejandro , Damasceno, Albertino , Espeche, Walter , Jose, Arun , Khan, Nadia , Kokubo, Yoshihiro , Maheshwari, Anuj , Marin, Marcos , More, Arun , Neupane, Dinesh , Nilsson, Peter , Patil, Mansi , Prabhakaran, Dorairaj , Ramirez, Agustin , Rodriguez, Pablo , Schlaich, Markus , Steckelings, Ulrike , Tomaszewski, Maciej , Unger, Thomas , Wainford, Richard , Wang, Jiguang , Williams, Bryan , Poulter, Neil , M. M. M. Investigators
- Date: 2020
- Type: Text , Journal article
- Relation: Hypertension Vol. 76, no. 2 (Aug 2020), p. 333-341
- Full Text:
- Reviewed:
- Description: Elevated blood pressure remains the single biggest risk factor contributing to the global burden of disease and mortality. May Measurement Month is an annual global screening campaign aiming to improve awareness of blood pressure at the individual and population level. Adults (>= 18 years) recruited through opportunistic sampling were screened at sites in 92 countries during May 2019. Ideally, 3 blood pressure readings were measured for each participant, and data on lifestyle factors and comorbidities were collected. Hypertension was defined as a systolic blood pressure >= 140 mm Hg, or a diastolic blood pressure >= 90 mm Hg (mean of the second and third readings) or taking antihypertensive medication. When necessary, multiple imputation was used to estimate participants' mean blood pressure. Mixed-effects models were used to evaluate associations between blood pressure and participant characteristics. Of 1 508 130 screenees 482 273 (32.0%) had never had a blood pressure measurement before and 513 337 (34.0%) had hypertension, of whom 58.7% were aware, and 54.7% were on antihypertensive medication. Of those on medication, 57.8% were controlled to <140/90 mm Hg, and 28.9% to <130/80 mm Hg. Of all those with hypertension, 31.7% were controlled to <140/90 mm Hg, and 350 825 (23.3%) participants had untreated or inadequately treated hypertension. Of those taking antihypertensive medication, half were taking only a single drug, and 25% reported using aspirin inappropriately. This survey is the largest ever synchronized and standardized contemporary compilation of global blood pressure data. This campaign is needed as a temporary substitute for systematic blood pressure screening in many countries worldwide.
- Authors: Beaney, Thomas , Schutte, Aletta , Stergiou, George , Borghi, Claudio , Burger, Dylan , Charchar, Fadi , Cro, Suzie , Diaz, Alejandro , Damasceno, Albertino , Espeche, Walter , Jose, Arun , Khan, Nadia , Kokubo, Yoshihiro , Maheshwari, Anuj , Marin, Marcos , More, Arun , Neupane, Dinesh , Nilsson, Peter , Patil, Mansi , Prabhakaran, Dorairaj , Ramirez, Agustin , Rodriguez, Pablo , Schlaich, Markus , Steckelings, Ulrike , Tomaszewski, Maciej , Unger, Thomas , Wainford, Richard , Wang, Jiguang , Williams, Bryan , Poulter, Neil , M. M. M. Investigators
- Date: 2020
- Type: Text , Journal article
- Relation: Hypertension Vol. 76, no. 2 (Aug 2020), p. 333-341
- Full Text:
- Reviewed:
- Description: Elevated blood pressure remains the single biggest risk factor contributing to the global burden of disease and mortality. May Measurement Month is an annual global screening campaign aiming to improve awareness of blood pressure at the individual and population level. Adults (>= 18 years) recruited through opportunistic sampling were screened at sites in 92 countries during May 2019. Ideally, 3 blood pressure readings were measured for each participant, and data on lifestyle factors and comorbidities were collected. Hypertension was defined as a systolic blood pressure >= 140 mm Hg, or a diastolic blood pressure >= 90 mm Hg (mean of the second and third readings) or taking antihypertensive medication. When necessary, multiple imputation was used to estimate participants' mean blood pressure. Mixed-effects models were used to evaluate associations between blood pressure and participant characteristics. Of 1 508 130 screenees 482 273 (32.0%) had never had a blood pressure measurement before and 513 337 (34.0%) had hypertension, of whom 58.7% were aware, and 54.7% were on antihypertensive medication. Of those on medication, 57.8% were controlled to <140/90 mm Hg, and 28.9% to <130/80 mm Hg. Of all those with hypertension, 31.7% were controlled to <140/90 mm Hg, and 350 825 (23.3%) participants had untreated or inadequately treated hypertension. Of those taking antihypertensive medication, half were taking only a single drug, and 25% reported using aspirin inappropriately. This survey is the largest ever synchronized and standardized contemporary compilation of global blood pressure data. This campaign is needed as a temporary substitute for systematic blood pressure screening in many countries worldwide.
Measurement of absolute copy number variation reveals association with essential hypertension
- Marques, Francine, Prestes, Priscilla, Pinheiro, Leonardo, Scurrah, Katrina, Emslie, Kerry, Tomaszewski, Maciej, Harrap, Stephen, Charchar, Fadi
- Authors: Marques, Francine , Prestes, Priscilla , Pinheiro, Leonardo , Scurrah, Katrina , Emslie, Kerry , Tomaszewski, Maciej , Harrap, Stephen , Charchar, Fadi
- Date: 2014
- Type: Text , Journal article
- Relation: BMC Medical Genomics Vol. 7, no. (2014), p. 1-8
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- Reviewed:
- Description: Background: The role of copy number variation (CNV) has been poorly explored in essential hypertension in part due to technical difficulties in accurately assessing absolute numbers of DNA copies. Droplet digital PCR (ddPCR) provides a powerful new approach to CNV quantitation. The aim of our study was to investigate whether CNVs located in regions previously associated with blood pressure (BP) variation in genome-wide association studies (GWAS) were associated with essential hypertension by the use of ddPCR. Methods: Using a "power of extreme" approach, we quantified nucleic acids using ddPCR in white subjects from the Victorian Family Heart Study with extremely high (n = 96) and low (n = 92) SBP, providing power equivalent to 1714 subjects selected at random. Results: A deletion of the CNVs esv27061 and esv2757747 on chromosome 1p13.2 was significantly more prevalent in extreme high BP subjects after adjustment for age, body mass index and sex (12.6% vs. 2.2%; P = 0.013). Conclusions: Our data suggests that CNVs within regions identified in previous GWAS may play a role in human essential hypertension.
- Authors: Marques, Francine , Prestes, Priscilla , Pinheiro, Leonardo , Scurrah, Katrina , Emslie, Kerry , Tomaszewski, Maciej , Harrap, Stephen , Charchar, Fadi
- Date: 2014
- Type: Text , Journal article
- Relation: BMC Medical Genomics Vol. 7, no. (2014), p. 1-8
- Full Text:
- Reviewed:
- Description: Background: The role of copy number variation (CNV) has been poorly explored in essential hypertension in part due to technical difficulties in accurately assessing absolute numbers of DNA copies. Droplet digital PCR (ddPCR) provides a powerful new approach to CNV quantitation. The aim of our study was to investigate whether CNVs located in regions previously associated with blood pressure (BP) variation in genome-wide association studies (GWAS) were associated with essential hypertension by the use of ddPCR. Methods: Using a "power of extreme" approach, we quantified nucleic acids using ddPCR in white subjects from the Victorian Family Heart Study with extremely high (n = 96) and low (n = 92) SBP, providing power equivalent to 1714 subjects selected at random. Results: A deletion of the CNVs esv27061 and esv2757747 on chromosome 1p13.2 was significantly more prevalent in extreme high BP subjects after adjustment for age, body mass index and sex (12.6% vs. 2.2%; P = 0.013). Conclusions: Our data suggests that CNVs within regions identified in previous GWAS may play a role in human essential hypertension.
MicroRNAs in a hypertrophic heart : From foetal life to adulthood
- Sadiq, Shahzad, Crowley, Tamsyn, Charchar, Fadi, Sanigorski, Andrew, Lewandowski, Paul
- Authors: Sadiq, Shahzad , Crowley, Tamsyn , Charchar, Fadi , Sanigorski, Andrew , Lewandowski, Paul
- Date: 2017
- Type: Text , Journal article
- Relation: Biological Reviews Vol. 92, no. 3 (2017), p. 1314-1331
- Full Text:
- Reviewed:
- Description: The heart is the first organ to form and undergoes adaptive remodelling with age. Ventricular hypertrophy is one such adaptation, which allows the heart to cope with an increase in cardiac demand. This adaptation is necessary as part of natural growth from foetal life to adulthood. It may also occur in response to resistance in blood flow due to various insults on the heart and vessels that accumulate with age. The heart can only compensate to this increase in workload to a certain extent without losing its functional architecture, ultimately resulting in heart failure. Many genes have been implicated in cardiac hypertrophy, however none have been shown conclusively to be responsible for pathological cardiac hypertrophy. MicroRNAs offer an alternative mechanism for cellular regulation by altering gene expression. Since 1993 when the function of a non-coding DNA sequence was first discovered in the model organism Caenorhabditis elegans, many microRNAs have been implicated in having a central role in numerous physiological and pathological cellular processes. The level of control these antisense oligonucleotides offer can often be exploited to manipulate the expression of target genes. Moreover, altered levels of microRNAs can serve as diagnostic biomarkers, with the prospect of diagnosing a disease process as early as during foetal life. Therefore, it is vital to ascertain and investigate the function of microRNAs that are involved in heart development and subsequent ventricular remodelling. Here we present an overview of the complicated network of microRNAs and their target genes that have previously been implicated in cardiogenesis and hypertrophy. It is interesting to note that microRNAs in both of these growth processes can be of possible remedial value to counter a similar disease pathophysiology.
- Authors: Sadiq, Shahzad , Crowley, Tamsyn , Charchar, Fadi , Sanigorski, Andrew , Lewandowski, Paul
- Date: 2017
- Type: Text , Journal article
- Relation: Biological Reviews Vol. 92, no. 3 (2017), p. 1314-1331
- Full Text:
- Reviewed:
- Description: The heart is the first organ to form and undergoes adaptive remodelling with age. Ventricular hypertrophy is one such adaptation, which allows the heart to cope with an increase in cardiac demand. This adaptation is necessary as part of natural growth from foetal life to adulthood. It may also occur in response to resistance in blood flow due to various insults on the heart and vessels that accumulate with age. The heart can only compensate to this increase in workload to a certain extent without losing its functional architecture, ultimately resulting in heart failure. Many genes have been implicated in cardiac hypertrophy, however none have been shown conclusively to be responsible for pathological cardiac hypertrophy. MicroRNAs offer an alternative mechanism for cellular regulation by altering gene expression. Since 1993 when the function of a non-coding DNA sequence was first discovered in the model organism Caenorhabditis elegans, many microRNAs have been implicated in having a central role in numerous physiological and pathological cellular processes. The level of control these antisense oligonucleotides offer can often be exploited to manipulate the expression of target genes. Moreover, altered levels of microRNAs can serve as diagnostic biomarkers, with the prospect of diagnosing a disease process as early as during foetal life. Therefore, it is vital to ascertain and investigate the function of microRNAs that are involved in heart development and subsequent ventricular remodelling. Here we present an overview of the complicated network of microRNAs and their target genes that have previously been implicated in cardiogenesis and hypertrophy. It is interesting to note that microRNAs in both of these growth processes can be of possible remedial value to counter a similar disease pathophysiology.
Molecular insights into genome-wide association studies of chronic kidney disease-defining traits
- Xu, Xiaoguang, Eales, James, Akbarov, Artur, Guo, Hui, Becker, Lorenz, Talavera, David, Ashraf, Fehzan, Nawaz, Jabran, Pramanik, Sanjeev, Bowes, John, Jiang, Xiao, Dormer, John, Denniff, Matthew, Antczak, Andrzej, Szulinska, Monika, Wise, Ingrid, Prestes, Priscilla, Glyda, Maciej, Bogdanski, Pawel, Zukowska-Szczechowska, Ewa, Berzuini, Carlo, Woolf, Adrian, Samani, Nilesh, Charchar, Fadi, Tomaszewski, Maciej
- Authors: Xu, Xiaoguang , Eales, James , Akbarov, Artur , Guo, Hui , Becker, Lorenz , Talavera, David , Ashraf, Fehzan , Nawaz, Jabran , Pramanik, Sanjeev , Bowes, John , Jiang, Xiao , Dormer, John , Denniff, Matthew , Antczak, Andrzej , Szulinska, Monika , Wise, Ingrid , Prestes, Priscilla , Glyda, Maciej , Bogdanski, Pawel , Zukowska-Szczechowska, Ewa , Berzuini, Carlo , Woolf, Adrian , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2018
- Type: Text , Journal article
- Relation: Nature communications Vol. 9, no. 1 (2018), p. 1-12
- Full Text:
- Reviewed:
- Description: Genome-wide association studies (GWAS) have identified >100 loci of chronic kidney disease-defining traits (CKD-dt). Molecular mechanisms underlying these associations remain elusive. Using 280 kidney transcriptomes and 9958 gene expression profiles from 44 non-renal tissues we uncover gene expression partners (eGenes) for 88.9% of CKD-dt GWAS loci. Through epigenomic chromatin segmentation analysis and variant effect prediction we annotate functional consequences to 74% of these loci. Our colocalisation analysis and Mendelian randomisation in >130,000 subjects demonstrate causal effects of three eGenes (NAT8B, CASP9 and MUC1) on estimated glomerular filtration rate. We identify a common alternative splice variant in MUC1 (a gene responsible for rare Mendelian form of kidney disease) and observe increased renal expression of a specific MUC1 mRNA isoform as a plausible molecular mechanism of the GWAS association signal. These data highlight the variants and genes underpinning the associations uncovered in GWAS of CKD-dt.
- Authors: Xu, Xiaoguang , Eales, James , Akbarov, Artur , Guo, Hui , Becker, Lorenz , Talavera, David , Ashraf, Fehzan , Nawaz, Jabran , Pramanik, Sanjeev , Bowes, John , Jiang, Xiao , Dormer, John , Denniff, Matthew , Antczak, Andrzej , Szulinska, Monika , Wise, Ingrid , Prestes, Priscilla , Glyda, Maciej , Bogdanski, Pawel , Zukowska-Szczechowska, Ewa , Berzuini, Carlo , Woolf, Adrian , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2018
- Type: Text , Journal article
- Relation: Nature communications Vol. 9, no. 1 (2018), p. 1-12
- Full Text:
- Reviewed:
- Description: Genome-wide association studies (GWAS) have identified >100 loci of chronic kidney disease-defining traits (CKD-dt). Molecular mechanisms underlying these associations remain elusive. Using 280 kidney transcriptomes and 9958 gene expression profiles from 44 non-renal tissues we uncover gene expression partners (eGenes) for 88.9% of CKD-dt GWAS loci. Through epigenomic chromatin segmentation analysis and variant effect prediction we annotate functional consequences to 74% of these loci. Our colocalisation analysis and Mendelian randomisation in >130,000 subjects demonstrate causal effects of three eGenes (NAT8B, CASP9 and MUC1) on estimated glomerular filtration rate. We identify a common alternative splice variant in MUC1 (a gene responsible for rare Mendelian form of kidney disease) and observe increased renal expression of a specific MUC1 mRNA isoform as a plausible molecular mechanism of the GWAS association signal. These data highlight the variants and genes underpinning the associations uncovered in GWAS of CKD-dt.
Noncoding genes on sex chromosomes and their function in sex determination, dosage compensation, male traits, and diseases
- Maier, Michelle, McInerney, Molly-Rose, Graves, Jennifer, Charchar, Fadi
- Authors: Maier, Michelle , McInerney, Molly-Rose , Graves, Jennifer , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article , Review
- Relation: Sexual Development Vol. 15, no. 5-6 (2021), p. 432-440
- Relation: http://purl.org/au-research/grants/nhmrc/1123472
- Full Text:
- Reviewed:
- Description: The mammalian Y chromosome has evolved in many species into a specialized chromosome that contributes to sex development among other male phenotypes. This function is well studied in terms of protein-coding genes. Less is known about the noncoding genome on the Y chromosome and its contribution to both sex development and other traits. Once considered junk genetic material, noncoding RNAs are now known to contribute to the regulation of gene expression and to play an important role in refining cellular functions. The prime examples are noncoding genes on the X chromosome, which mitigate the differential dosage of genes on sex chromosomes. Here, we discuss the evolution of noncoding RNAs on the Y chromosome and the emerging evidence of how micro, long, and circular noncoding RNAs transcribed from the Y chromosome contribute to sex differentiation. We briefly touch on emerging evidence that these noncoding RNAs also contribute to some other important clinical phenotypes in humans. © 2021 S. Karger AG. All rights reserved.
- Authors: Maier, Michelle , McInerney, Molly-Rose , Graves, Jennifer , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article , Review
- Relation: Sexual Development Vol. 15, no. 5-6 (2021), p. 432-440
- Relation: http://purl.org/au-research/grants/nhmrc/1123472
- Full Text:
- Reviewed:
- Description: The mammalian Y chromosome has evolved in many species into a specialized chromosome that contributes to sex development among other male phenotypes. This function is well studied in terms of protein-coding genes. Less is known about the noncoding genome on the Y chromosome and its contribution to both sex development and other traits. Once considered junk genetic material, noncoding RNAs are now known to contribute to the regulation of gene expression and to play an important role in refining cellular functions. The prime examples are noncoding genes on the X chromosome, which mitigate the differential dosage of genes on sex chromosomes. Here, we discuss the evolution of noncoding RNAs on the Y chromosome and the emerging evidence of how micro, long, and circular noncoding RNAs transcribed from the Y chromosome contribute to sex differentiation. We briefly touch on emerging evidence that these noncoding RNAs also contribute to some other important clinical phenotypes in humans. © 2021 S. Karger AG. All rights reserved.
Plasma lipocalin-2/NGAL is stable over 12 weeks and is not modulated by exercise or dieting
- Nakai, Michael, Prestes, Priscilla, O’Brien, Brendan, Charchar, Fadi, Marques, Francine
- Authors: Nakai, Michael , Prestes, Priscilla , O’Brien, Brendan , Charchar, Fadi , Marques, Francine
- Date: 2021
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
- Full Text:
- Reviewed:
- Description: Amongst other immune cells, neutrophils play a key role in systemic inflammation leading to cardiovascular disease and can release inflammatory factors, including lipocalin-2 (LCN2). LCN2 drives cardiac hypertrophy and plays a role in maladaptive remodelling of the heart and has been associated with renal injury. While lifestyle factors such as diet and exercise are known to attenuate low-grade inflammation, their ability to modulate plasma LCN2 levels is unknown. Forty-eight endurance athletes and 52 controls (18–55 years) underwent measurement for various cardiovascular health indicators, along with plasma LCN2 concentration. No significant difference in LCN2 concentration was seen between the two groups. LCN2 was a very weak predictor or absent from models describing blood pressures or predicting athlete status. In another cohort, 57 non-diabetic overweight or obese men and post-menopausal women who fulfilled Adult Treatment Panel III metabolic syndrome criteria were randomly allocated into either a control, modified Dietary Approaches to Stop Hypertension (DASH) diet, or DASH and exercise group. Pre- and post-intervention demographic, cardiovascular health indicators, and plasma LCN2 expression were measured in each individual. While BMI fell in intervention groups, LCN2 levels remained unchanged within and between all groups, as illustrated by strong correlations between LCN2 concentrations pre- and 12 weeks post-intervention (r = 0.743, P < 0.0001). This suggests that circulating LCN2 expression are stable over a period of at least 12 weeks and is not modifiable by diet and exercise. © 2021, The Author(s). *Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Priscilla Prestes, Brendan O'Brien, Fadi Charchar and Francine Marques” is provided in this record** .
- Authors: Nakai, Michael , Prestes, Priscilla , O’Brien, Brendan , Charchar, Fadi , Marques, Francine
- Date: 2021
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
- Full Text:
- Reviewed:
- Description: Amongst other immune cells, neutrophils play a key role in systemic inflammation leading to cardiovascular disease and can release inflammatory factors, including lipocalin-2 (LCN2). LCN2 drives cardiac hypertrophy and plays a role in maladaptive remodelling of the heart and has been associated with renal injury. While lifestyle factors such as diet and exercise are known to attenuate low-grade inflammation, their ability to modulate plasma LCN2 levels is unknown. Forty-eight endurance athletes and 52 controls (18–55 years) underwent measurement for various cardiovascular health indicators, along with plasma LCN2 concentration. No significant difference in LCN2 concentration was seen between the two groups. LCN2 was a very weak predictor or absent from models describing blood pressures or predicting athlete status. In another cohort, 57 non-diabetic overweight or obese men and post-menopausal women who fulfilled Adult Treatment Panel III metabolic syndrome criteria were randomly allocated into either a control, modified Dietary Approaches to Stop Hypertension (DASH) diet, or DASH and exercise group. Pre- and post-intervention demographic, cardiovascular health indicators, and plasma LCN2 expression were measured in each individual. While BMI fell in intervention groups, LCN2 levels remained unchanged within and between all groups, as illustrated by strong correlations between LCN2 concentrations pre- and 12 weeks post-intervention (r = 0.743, P < 0.0001). This suggests that circulating LCN2 expression are stable over a period of at least 12 weeks and is not modifiable by diet and exercise. © 2021, The Author(s). *Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Priscilla Prestes, Brendan O'Brien, Fadi Charchar and Francine Marques” is provided in this record** .
Plasma proteomics of renal function: A transethnic meta-analysis and mendelian randomization study
- Matías-García, Pamela, Wilson, Rory, Guo, Qi, Zaghlool, Shaza, Charchar, Fadi
- Authors: Matías-García, Pamela , Wilson, Rory , Guo, Qi , Zaghlool, Shaza , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Journal of the American Society of Nephrology Vol. 32, no. 7 (2021), p. 1747-1763
- Full Text:
- Reviewed:
- Description: Background Studies on the relationship between renal function and the human plasma proteome have identified several potential biomarkers. However, investigations have been conducted largely in European populations, and causality of the associations between plasma proteins and kidney function has never been addressed. Methods A cross-sectional study of 993 plasma proteins among 2882 participants in four studies of European and admixed ancestries (KORA, INTERVAL, HUNT, QMDiab) identified transethnic associations between eGFR/CKD and proteomic biomarkers. For the replicated associations, two-sample bidirectional Mendelian randomization (MR) was used to investigate potential causal relationships. Publicly available datasets and transcriptomic data from independent studies were used to examine the association between gene expression in kidney tissue and eGFR. Results In total, 57 plasma proteins were associated with eGFR, including one novel protein. Of these, 23 were additionally associated with CKD. The strongest inferred causal effect was the positive effect of eGFR on testican-2, in line with the known biological role of this protein and the expression of its protein-coding gene (SPOCK2) in renal tissue. We also observed suggestive evidence of an effect of melanoma inhibitory activity (MIA), carbonic anhydrase III, and cystatin-M on eGFR. Conclusions In a discovery-replication setting, we identified 57 proteins transethnically associated with eGFR. The revealed causal relationships are an important stepping stone in establishing testican-2 as a clinically relevant physiological marker of kidney disease progression, and point to additional proteins warranting further investigation. © 2021 by the American Society of Nephrology
- Authors: Matías-García, Pamela , Wilson, Rory , Guo, Qi , Zaghlool, Shaza , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Journal of the American Society of Nephrology Vol. 32, no. 7 (2021), p. 1747-1763
- Full Text:
- Reviewed:
- Description: Background Studies on the relationship between renal function and the human plasma proteome have identified several potential biomarkers. However, investigations have been conducted largely in European populations, and causality of the associations between plasma proteins and kidney function has never been addressed. Methods A cross-sectional study of 993 plasma proteins among 2882 participants in four studies of European and admixed ancestries (KORA, INTERVAL, HUNT, QMDiab) identified transethnic associations between eGFR/CKD and proteomic biomarkers. For the replicated associations, two-sample bidirectional Mendelian randomization (MR) was used to investigate potential causal relationships. Publicly available datasets and transcriptomic data from independent studies were used to examine the association between gene expression in kidney tissue and eGFR. Results In total, 57 plasma proteins were associated with eGFR, including one novel protein. Of these, 23 were additionally associated with CKD. The strongest inferred causal effect was the positive effect of eGFR on testican-2, in line with the known biological role of this protein and the expression of its protein-coding gene (SPOCK2) in renal tissue. We also observed suggestive evidence of an effect of melanoma inhibitory activity (MIA), carbonic anhydrase III, and cystatin-M on eGFR. Conclusions In a discovery-replication setting, we identified 57 proteins transethnically associated with eGFR. The revealed causal relationships are an important stepping stone in establishing testican-2 as a clinically relevant physiological marker of kidney disease progression, and point to additional proteins warranting further investigation. © 2021 by the American Society of Nephrology
Reduced renal function may explain the higher prevalence of hyperuricemia in older people
- Wang, Yutang, Zhang, Wanlin, Qian, Tingting, Sun, Hui, Xu, Qun, Hou, Xujuan, Hu, Wenqi, Zhang, Guang, Drummond, Grant, Sobey, Chris, Charchar, Fadi, Golledge, Jonathan, Yang, Guang
- Authors: Wang, Yutang , Zhang, Wanlin , Qian, Tingting , Sun, Hui , Xu, Qun , Hou, Xujuan , Hu, Wenqi , Zhang, Guang , Drummond, Grant , Sobey, Chris , Charchar, Fadi , Golledge, Jonathan , Yang, Guang
- Date: 2021
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: This study aimed to investigate the contribution of renal dysfunction to enhanced hyperuricemia prevalence in older people. A cohort of 13,288 Chinese people aged between 40 and 95 years were recruited from January to May 2019. Serum uric acid concentration and estimated glomerular filtration rate [eGFR] were measured. The associations between age or eGFR and serum uric acid or hyperuricemia were analyzed using linear or binary logistic regression adjusting for risk factors. Uric acid concentration and prevalence of hyperuricemia were greater in older participants. Adjustment for reduced renal function (eGFR < 60 mL/min/1.73 m2) eliminated the associations between older age and higher uric acid concentration and between older age and higher prevalence of hyperuricemia diagnosis, whereas adjustment for other risk factors did not change those associations. Lower eGFR was associated with higher uric acid concentration both before (β = − 0.296, P < 0.001) and after adjustment for age (β = − 0.313, P < 0.001). Reduced renal function was associated with hyperuricemia diagnosis both before (odds ratio, OR, 3.64; 95% CI 3.10–4.28; P < 0.001) and after adjustment for age (adjusted OR, 3.82; 95% CI 3.22–4.54; P < 0.001). Mean serum uric acid and prevalence of hyperuricemia were higher in people with eGFR < 60 mL/min/1.73 m2 than those with eGFR ≥ 60 mL/min/1.73 m2. The prevalence of reduced renal function increased with older age (P < 0.001). This study suggests that reduced renal function can explain the increased uric acid levels and hyperuricemia diagnoses in older people. © 2021, The Author(s).
- Authors: Wang, Yutang , Zhang, Wanlin , Qian, Tingting , Sun, Hui , Xu, Qun , Hou, Xujuan , Hu, Wenqi , Zhang, Guang , Drummond, Grant , Sobey, Chris , Charchar, Fadi , Golledge, Jonathan , Yang, Guang
- Date: 2021
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: This study aimed to investigate the contribution of renal dysfunction to enhanced hyperuricemia prevalence in older people. A cohort of 13,288 Chinese people aged between 40 and 95 years were recruited from January to May 2019. Serum uric acid concentration and estimated glomerular filtration rate [eGFR] were measured. The associations between age or eGFR and serum uric acid or hyperuricemia were analyzed using linear or binary logistic regression adjusting for risk factors. Uric acid concentration and prevalence of hyperuricemia were greater in older participants. Adjustment for reduced renal function (eGFR < 60 mL/min/1.73 m2) eliminated the associations between older age and higher uric acid concentration and between older age and higher prevalence of hyperuricemia diagnosis, whereas adjustment for other risk factors did not change those associations. Lower eGFR was associated with higher uric acid concentration both before (β = − 0.296, P < 0.001) and after adjustment for age (β = − 0.313, P < 0.001). Reduced renal function was associated with hyperuricemia diagnosis both before (odds ratio, OR, 3.64; 95% CI 3.10–4.28; P < 0.001) and after adjustment for age (adjusted OR, 3.82; 95% CI 3.22–4.54; P < 0.001). Mean serum uric acid and prevalence of hyperuricemia were higher in people with eGFR < 60 mL/min/1.73 m2 than those with eGFR ≥ 60 mL/min/1.73 m2. The prevalence of reduced renal function increased with older age (P < 0.001). This study suggests that reduced renal function can explain the increased uric acid levels and hyperuricemia diagnoses in older people. © 2021, The Author(s).
Relationship between anti-DFS70 autoantibodies and oxidative stress
- Krzemień, Pawel, Kasperczyk, Slawomir, Banach, Maciej, Kasperczyk, Aleksandra, Dobrakowski, Michal, Tomasik, Tomasz, Windak, Adam, Mastej, Miroslaw, Catapano, Alberico, Ray, Kausik, Mikhailidis, Dimitri, Toth, Peter, Howard, George, Lip, Gregory, Tomaszewski, Maciej, Charchar, Fadi, Sattar, Naveed, Williams, Bryan, MacDonald, Thomas, Penson, Peter, Jóźwiak, J, Al-Shaer, B., Andrusewicz, W., Andrzejczuk-Rosa, M., Anusz-Gaszewska, E., Bagińska, A., Balawajder, P., Bańka, G., Barańska-Skubisz, E., Barbara Przyczyna, B.
- Authors: Krzemień, Pawel , Kasperczyk, Slawomir , Banach, Maciej , Kasperczyk, Aleksandra , Dobrakowski, Michal , Tomasik, Tomasz , Windak, Adam , Mastej, Miroslaw , Catapano, Alberico , Ray, Kausik , Mikhailidis, Dimitri , Toth, Peter , Howard, George , Lip, Gregory , Tomaszewski, Maciej , Charchar, Fadi , Sattar, Naveed , Williams, Bryan , MacDonald, Thomas , Penson, Peter , Jóźwiak, J , Al-Shaer, B. , Andrusewicz, W. , Andrzejczuk-Rosa, M. , Anusz-Gaszewska, E. , Bagińska, A. , Balawajder, P. , Bańka, G. , Barańska-Skubisz, E. , Barbara Przyczyna, B.
- Date: 2022
- Type: Text , Journal article
- Relation: Biomarker Insights Vol. 17, no. (2022), p.
- Full Text:
- Reviewed:
- Description: Background: The anti-DFS70 autoantibodies are one of the most commonly and widely described agent of unknown clinical significance, frequently detected in healthy individuals. It is not known whether the DFS70 autoantibodies are protective or pathogenic. One of the factors suspected of inducing the formation of anti-DFS70 antibodies is increased oxidative stress. We evaluated the coexistence of anti-DFS70 antibodies with selected markers of oxidative stress and investigated whether these antibodies could be considered as indirect markers of oxidative stress. Methods: The intensity of oxidative stress was measured in all samples via indices of free-radical damage to lipids and proteins such as total oxidant status (TOS), concentrations of lipid hydroperoxides (LPH), lipofuscin (LPS), and malondialdehyde (MDA). The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid concentration (UA), were also measured, as well as the activity of superoxide dismutase (SOD). Based on TOS and TAS values, the oxidative stress index (OSI) was calculated. All samples were also tested with indirect immunofluorescence assay (IFA) and 357 samples were selected for direct monospecific anti DFS70 enzyme-linked immunosorbent assay (ELISA) testing. Results: The anti-DFS70 antibodies were confirmed by ELISA test in 21.29% of samples. Compared with anti-DFS70 negative samples we observed 23% lower concentration of LPH (P =.038) and 11% lower concentration of UA (P =.005). TOS was 20% lower (P =.014). The activity of SOD was up to 5% higher (P =.037). The Pearson correlation showed weak negative correlation for LPH, UA, and TOS and a weak positive correlation for SOD activity. Conclusion: In samples positive for the anti-DFS70 antibody a decreased level of oxidative stress was observed, especially in the case of samples with a high antibody titer. Anti-DFS70 antibodies can be considered as an indirect marker of reduced oxidative stress or a marker indicating the recent intensification of antioxidant processes. © The Author(s) 2022. **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliate “Fadi Charchar” is provided in this record**
- Authors: Krzemień, Pawel , Kasperczyk, Slawomir , Banach, Maciej , Kasperczyk, Aleksandra , Dobrakowski, Michal , Tomasik, Tomasz , Windak, Adam , Mastej, Miroslaw , Catapano, Alberico , Ray, Kausik , Mikhailidis, Dimitri , Toth, Peter , Howard, George , Lip, Gregory , Tomaszewski, Maciej , Charchar, Fadi , Sattar, Naveed , Williams, Bryan , MacDonald, Thomas , Penson, Peter , Jóźwiak, J , Al-Shaer, B. , Andrusewicz, W. , Andrzejczuk-Rosa, M. , Anusz-Gaszewska, E. , Bagińska, A. , Balawajder, P. , Bańka, G. , Barańska-Skubisz, E. , Barbara Przyczyna, B.
- Date: 2022
- Type: Text , Journal article
- Relation: Biomarker Insights Vol. 17, no. (2022), p.
- Full Text:
- Reviewed:
- Description: Background: The anti-DFS70 autoantibodies are one of the most commonly and widely described agent of unknown clinical significance, frequently detected in healthy individuals. It is not known whether the DFS70 autoantibodies are protective or pathogenic. One of the factors suspected of inducing the formation of anti-DFS70 antibodies is increased oxidative stress. We evaluated the coexistence of anti-DFS70 antibodies with selected markers of oxidative stress and investigated whether these antibodies could be considered as indirect markers of oxidative stress. Methods: The intensity of oxidative stress was measured in all samples via indices of free-radical damage to lipids and proteins such as total oxidant status (TOS), concentrations of lipid hydroperoxides (LPH), lipofuscin (LPS), and malondialdehyde (MDA). The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid concentration (UA), were also measured, as well as the activity of superoxide dismutase (SOD). Based on TOS and TAS values, the oxidative stress index (OSI) was calculated. All samples were also tested with indirect immunofluorescence assay (IFA) and 357 samples were selected for direct monospecific anti DFS70 enzyme-linked immunosorbent assay (ELISA) testing. Results: The anti-DFS70 antibodies were confirmed by ELISA test in 21.29% of samples. Compared with anti-DFS70 negative samples we observed 23% lower concentration of LPH (P =.038) and 11% lower concentration of UA (P =.005). TOS was 20% lower (P =.014). The activity of SOD was up to 5% higher (P =.037). The Pearson correlation showed weak negative correlation for LPH, UA, and TOS and a weak positive correlation for SOD activity. Conclusion: In samples positive for the anti-DFS70 antibody a decreased level of oxidative stress was observed, especially in the case of samples with a high antibody titer. Anti-DFS70 antibodies can be considered as an indirect marker of reduced oxidative stress or a marker indicating the recent intensification of antioxidant processes. © The Author(s) 2022. **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliate “Fadi Charchar” is provided in this record**
Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure
- Tomaszewski, Maciej, Eales, James, Denniff, Matthew, Myers, Stephen, Chew, Guatsiew, Nelson, Christopher, Christofidou, Paraskevi, Desai, Aishwarya, Büsst, Cara, Wojnar, Lukasz, Musialik, Katarzyna, Jozwiak, Jacek, Debiec, Radoslaw, Dominiczak, Anna, Navis, Gerjan, van Gilst, Wiek, van der Harst, Pim, Samani, Nilesh, Harrap, Stephen, Bogdanski, Pawel, Zukowska-Szczechowska, Ewa, Charchar, Fadi
- Authors: Tomaszewski, Maciej , Eales, James , Denniff, Matthew , Myers, Stephen , Chew, Guatsiew , Nelson, Christopher , Christofidou, Paraskevi , Desai, Aishwarya , Büsst, Cara , Wojnar, Lukasz , Musialik, Katarzyna , Jozwiak, Jacek , Debiec, Radoslaw , Dominiczak, Anna , Navis, Gerjan , van Gilst, Wiek , van der Harst, Pim , Samani, Nilesh , Harrap, Stephen , Bogdanski, Pawel , Zukowska-Szczechowska, Ewa , Charchar, Fadi
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of the American Society of Nephrology Vol. 26, no. 12 (2015), p. 3151-3160
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
- Reviewed:
- Description: The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65 x10(-5)) and diastolic BP (P=7.61 x10(-3)) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0x10(-3)). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, reninangiotensin cascade, and sodium handling network may explain the association between FGF1 and BP.
- Authors: Tomaszewski, Maciej , Eales, James , Denniff, Matthew , Myers, Stephen , Chew, Guatsiew , Nelson, Christopher , Christofidou, Paraskevi , Desai, Aishwarya , Büsst, Cara , Wojnar, Lukasz , Musialik, Katarzyna , Jozwiak, Jacek , Debiec, Radoslaw , Dominiczak, Anna , Navis, Gerjan , van Gilst, Wiek , van der Harst, Pim , Samani, Nilesh , Harrap, Stephen , Bogdanski, Pawel , Zukowska-Szczechowska, Ewa , Charchar, Fadi
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of the American Society of Nephrology Vol. 26, no. 12 (2015), p. 3151-3160
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
- Reviewed:
- Description: The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65 x10(-5)) and diastolic BP (P=7.61 x10(-3)) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0x10(-3)). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, reninangiotensin cascade, and sodium handling network may explain the association between FGF1 and BP.
Renal nerves contribute to hypertension in Schlager BPH/2J mice
- Gueguen, Cindy, Jackson, Kristy, Marques, Francine, Eikelis, Nina, Phillips, Sarah, Stevenson, Emily, Charchar, Fadi, Lambert, Gavin, Davern, Pamela, Head, Geoffrey
- Authors: Gueguen, Cindy , Jackson, Kristy , Marques, Francine , Eikelis, Nina , Phillips, Sarah , Stevenson, Emily , Charchar, Fadi , Lambert, Gavin , Davern, Pamela , Head, Geoffrey
- Date: 2019
- Type: Text , Journal article
- Relation: Hypertension Research Vol. 42, no. 3 (2019), p. 306-318
- Full Text:
- Reviewed:
- Description: Schlager mice (BPH/2J) are hypertensive due to a greater contribution of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS). The kidneys of BPH/2J are hyper-innervated suggesting renal nerves may contribute to the hypertension. We therefore determined the effect of bilateral renal denervation (RD) on hypertension in BPH/2J. Mean arterial pressure (MAP) was measured by radiotelemetry before and for 3 weeks after RD in BPH/2J and BPN/3J. The effects of pentolinium and enalaprilat were examined to determine the contribution of the SNS and RAS, respectively. After 3 weeks, MAP was −10.9 ± 2.1 mmHg lower in RD BPH/2J compared to baseline and −2.1 ± 2.2 mmHg in sham BPH/2J (P < 0.001, n = 8–10). RD had no effect in BPN/3J (P > 0.1). The depressor response to pentolinium was greater in BPH/2J than BPN/3J, but in both cases the response in RD mice was similar to sham. Enalaprilat decreased MAP more in RD BPH/2J compared to sham (−12 vs −3 mmHg, P < 0.001) but had no effect in BPN/3J. RD reduced renal noradrenaline in both strains but more so in BPH/2J. RD reduced renin mRNA and protein, but not plasma renin in BPH/2J to levels comparable with BPN/3J mice. We conclude that renal nerves contribute to hypertension in BPH mice as RD induced a sustained fall in MAP, which was associated with a reduction of intrarenal renin expression. The lack of inhibition of the depressor effects of pentolinium and enalaprilat by RD suggests that vasoconstrictor effects of the SNS or RAS are not involved.
- Authors: Gueguen, Cindy , Jackson, Kristy , Marques, Francine , Eikelis, Nina , Phillips, Sarah , Stevenson, Emily , Charchar, Fadi , Lambert, Gavin , Davern, Pamela , Head, Geoffrey
- Date: 2019
- Type: Text , Journal article
- Relation: Hypertension Research Vol. 42, no. 3 (2019), p. 306-318
- Full Text:
- Reviewed:
- Description: Schlager mice (BPH/2J) are hypertensive due to a greater contribution of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS). The kidneys of BPH/2J are hyper-innervated suggesting renal nerves may contribute to the hypertension. We therefore determined the effect of bilateral renal denervation (RD) on hypertension in BPH/2J. Mean arterial pressure (MAP) was measured by radiotelemetry before and for 3 weeks after RD in BPH/2J and BPN/3J. The effects of pentolinium and enalaprilat were examined to determine the contribution of the SNS and RAS, respectively. After 3 weeks, MAP was −10.9 ± 2.1 mmHg lower in RD BPH/2J compared to baseline and −2.1 ± 2.2 mmHg in sham BPH/2J (P < 0.001, n = 8–10). RD had no effect in BPN/3J (P > 0.1). The depressor response to pentolinium was greater in BPH/2J than BPN/3J, but in both cases the response in RD mice was similar to sham. Enalaprilat decreased MAP more in RD BPH/2J compared to sham (−12 vs −3 mmHg, P < 0.001) but had no effect in BPN/3J. RD reduced renal noradrenaline in both strains but more so in BPH/2J. RD reduced renin mRNA and protein, but not plasma renin in BPH/2J to levels comparable with BPN/3J mice. We conclude that renal nerves contribute to hypertension in BPH mice as RD induced a sustained fall in MAP, which was associated with a reduction of intrarenal renin expression. The lack of inhibition of the depressor effects of pentolinium and enalaprilat by RD suggests that vasoconstrictor effects of the SNS or RAS are not involved.
Renin-angiotensin system inhibitors in patients With COVID-19 : a meta-analysis of randomized controlled trials led by the International Society of Hypertension
- Gnanenthiran, Sonali, Borghi, Claudio, Burger, Dylan, Caramelli, Bruno, Charchar, Fadi, Chirinos, Julio, Cohen, Jordana, Cremer, Antoine, Di Tanna, Gian, Duvignaud, Alexandre, Freilich, Daniel, Gommans, D., Gracia-Ramos, Abraham, Murray, Thomas, Pelorosso, Facundo, Poulter, Neil, Puskarich, Michael, Rizas, Konstantinos, Rothlin, Rodolfo, Schlaich, Markus, Schreinlecher, Michael, Steckelings, Ulrike, Sharma, Abhinav, Stergiou, George, Tignanelli, Christopher, Tomaszewski, Maciej, Unger, Thomas, van Kimmenade, Roland, Wainford, Richard, Williams, Bryan, Rodgers, Anthony, Schutte, Aletta
- Authors: Gnanenthiran, Sonali , Borghi, Claudio , Burger, Dylan , Caramelli, Bruno , Charchar, Fadi , Chirinos, Julio , Cohen, Jordana , Cremer, Antoine , Di Tanna, Gian , Duvignaud, Alexandre , Freilich, Daniel , Gommans, D. , Gracia-Ramos, Abraham , Murray, Thomas , Pelorosso, Facundo , Poulter, Neil , Puskarich, Michael , Rizas, Konstantinos , Rothlin, Rodolfo , Schlaich, Markus , Schreinlecher, Michael , Steckelings, Ulrike , Sharma, Abhinav , Stergiou, George , Tignanelli, Christopher , Tomaszewski, Maciej , Unger, Thomas , van Kimmenade, Roland , Wainford, Richard , Williams, Bryan , Rodgers, Anthony , Schutte, Aletta
- Date: 2022
- Type: Text , Journal article
- Relation: Journal of the American Heart Association Vol. 11, no. 17 (2022), p.
- Full Text:
- Reviewed:
- Description: BACKGROUND: Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin-angiotensin system inhibitors (RASi) in adults with COVID-19. We therefore performed a meta-analysis to assess the safety and efficacy of RASi in adults with COVID-19. METHODS AND RESULTS: MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Controlled Trial Register were searched for randomized controlled trials that randomly assigned patients with COVID-19 to RASi continuation/commencement versus no RASi therapy. The primary outcome was all-cause mortality at ≤30 days. A total of 14 randomized controlled trials met the inclusion criteria and enrolled 1838 participants (aged 59 years, 58% men, mean follow-up 26 days). Of the trials, 11 contributed data. We found no effect of RASi versus control on all-cause mortality (7.2% versus 7.5%; relative risk [RR], 0.95; [95% CI, 0.69–1.30]) either overall or in subgroups defined by COVID-19 severity or trial type. Network meta-analysis identified no difference between angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers. RASi users had a nonsignificant reduction in acute myocardial infarction (2.1% versus 3.6%; RR, 0.59; [95% CI, 0.33–1.06]), but increased risk of acute kidney injury (7.0% versus 3.6%; RR, 1.82; [95% CI, 1.05– 3.16]), in trials that initiated and continued RASi. There was no increase in need for dialysis or differences in congestive cardiac failure, cerebrovascular events, venous thromboembolism, hospitalization, intensive care admission, inotropes, or mechanical ventilation. CONCLUSIONS: This meta-analysis of randomized controlled trials evaluating angiotensin-converting enzyme inhibitors/angio-tensin II receptor blockers versus control in patients with COVID-19 found no difference in all-cause mortality, a borderline decrease in myocardial infarction, and an increased risk of acute kidney injury with RASi. Our findings provide strong evidence that RASi can be used safely in patients with COVID-19. © 2022 The Authors.
- Description: BACKGROUND: Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin-angiotensin system inhibitors (RASi) in adults with COVID-19. We therefore performed a meta-analysis to assess the safety and efficacy of RASi in adults with COVID-19. METHODS AND RESULTS: MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Controlled Trial Register were searched for randomized controlled trials that randomly assigned patients with COVID-19 to RASi continuation/commencement versus no RASi therapy. The primary outcome was all-cause mortality at
- Authors: Gnanenthiran, Sonali , Borghi, Claudio , Burger, Dylan , Caramelli, Bruno , Charchar, Fadi , Chirinos, Julio , Cohen, Jordana , Cremer, Antoine , Di Tanna, Gian , Duvignaud, Alexandre , Freilich, Daniel , Gommans, D. , Gracia-Ramos, Abraham , Murray, Thomas , Pelorosso, Facundo , Poulter, Neil , Puskarich, Michael , Rizas, Konstantinos , Rothlin, Rodolfo , Schlaich, Markus , Schreinlecher, Michael , Steckelings, Ulrike , Sharma, Abhinav , Stergiou, George , Tignanelli, Christopher , Tomaszewski, Maciej , Unger, Thomas , van Kimmenade, Roland , Wainford, Richard , Williams, Bryan , Rodgers, Anthony , Schutte, Aletta
- Date: 2022
- Type: Text , Journal article
- Relation: Journal of the American Heart Association Vol. 11, no. 17 (2022), p.
- Full Text:
- Reviewed:
- Description: BACKGROUND: Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin-angiotensin system inhibitors (RASi) in adults with COVID-19. We therefore performed a meta-analysis to assess the safety and efficacy of RASi in adults with COVID-19. METHODS AND RESULTS: MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Controlled Trial Register were searched for randomized controlled trials that randomly assigned patients with COVID-19 to RASi continuation/commencement versus no RASi therapy. The primary outcome was all-cause mortality at ≤30 days. A total of 14 randomized controlled trials met the inclusion criteria and enrolled 1838 participants (aged 59 years, 58% men, mean follow-up 26 days). Of the trials, 11 contributed data. We found no effect of RASi versus control on all-cause mortality (7.2% versus 7.5%; relative risk [RR], 0.95; [95% CI, 0.69–1.30]) either overall or in subgroups defined by COVID-19 severity or trial type. Network meta-analysis identified no difference between angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers. RASi users had a nonsignificant reduction in acute myocardial infarction (2.1% versus 3.6%; RR, 0.59; [95% CI, 0.33–1.06]), but increased risk of acute kidney injury (7.0% versus 3.6%; RR, 1.82; [95% CI, 1.05– 3.16]), in trials that initiated and continued RASi. There was no increase in need for dialysis or differences in congestive cardiac failure, cerebrovascular events, venous thromboembolism, hospitalization, intensive care admission, inotropes, or mechanical ventilation. CONCLUSIONS: This meta-analysis of randomized controlled trials evaluating angiotensin-converting enzyme inhibitors/angio-tensin II receptor blockers versus control in patients with COVID-19 found no difference in all-cause mortality, a borderline decrease in myocardial infarction, and an increased risk of acute kidney injury with RASi. Our findings provide strong evidence that RASi can be used safely in patients with COVID-19. © 2022 The Authors.
- Description: BACKGROUND: Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin-angiotensin system inhibitors (RASi) in adults with COVID-19. We therefore performed a meta-analysis to assess the safety and efficacy of RASi in adults with COVID-19. METHODS AND RESULTS: MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Controlled Trial Register were searched for randomized controlled trials that randomly assigned patients with COVID-19 to RASi continuation/commencement versus no RASi therapy. The primary outcome was all-cause mortality at
Salt Loading in Canola Oil Fed SHRSP Rats Induces Endothelial Dysfunction
- Papazzo, Annateresa, Conlan, Xavier, Lexis, Louise, Charchar, Fadi, Lewandowski, Paul
- Authors: Papazzo, Annateresa , Conlan, Xavier , Lexis, Louise , Charchar, Fadi , Lewandowski, Paul
- Date: 2013
- Type: Text , Journal article
- Relation: PLoS ONE Vol. 8, no. 6 (2013), p.
- Full Text:
- Reviewed:
- Description: This study aimed to determine if 50 days of canola oil intake in the absence or presence of salt loading affects: (1) antioxidant and oxidative stress markers, (2) aortic mRNA of NADPH oxidase (NOX) subunits and superoxide dismutase (SOD) isoforms and (3) endothelial function in SHRSP rats. SHRSP rats were fed a diet containing 10 wt/wt% soybean oil or 10 wt/wt% canola oil, and given tap water or water containing 1% NaCl for 50 days. Without salt, canola oil significantly increased RBC SOD, plasma cholesterol and triglycerides, aortic p22phox, NOX2 and CuZn-SOD mRNA, and decreased RBC glutathione peroxidase activity. With salt, canola oil reduced RBC SOD and catalase activity, LDL-C, and p22phox mRNA compared with canola oil alone, whereas plasma malondialdehyde (MDA) was reduced and RBC MDA and LDL-C were higher. With salt, the canola oil group had significantly reduced endothelium-dependent vasodilating responses to ACh and contractile responses to norepinephrine compared with the canola oil group without salt and to the WKY rats. These results indicate that ingestion of canola oil increases O2 - generation, and that canola oil ingestion in combination with salt leads to endothelial dysfunction in the SHRSP model. © 2013 Papazzo et al.
- Description: 2003011096
- Authors: Papazzo, Annateresa , Conlan, Xavier , Lexis, Louise , Charchar, Fadi , Lewandowski, Paul
- Date: 2013
- Type: Text , Journal article
- Relation: PLoS ONE Vol. 8, no. 6 (2013), p.
- Full Text:
- Reviewed:
- Description: This study aimed to determine if 50 days of canola oil intake in the absence or presence of salt loading affects: (1) antioxidant and oxidative stress markers, (2) aortic mRNA of NADPH oxidase (NOX) subunits and superoxide dismutase (SOD) isoforms and (3) endothelial function in SHRSP rats. SHRSP rats were fed a diet containing 10 wt/wt% soybean oil or 10 wt/wt% canola oil, and given tap water or water containing 1% NaCl for 50 days. Without salt, canola oil significantly increased RBC SOD, plasma cholesterol and triglycerides, aortic p22phox, NOX2 and CuZn-SOD mRNA, and decreased RBC glutathione peroxidase activity. With salt, canola oil reduced RBC SOD and catalase activity, LDL-C, and p22phox mRNA compared with canola oil alone, whereas plasma malondialdehyde (MDA) was reduced and RBC MDA and LDL-C were higher. With salt, the canola oil group had significantly reduced endothelium-dependent vasodilating responses to ACh and contractile responses to norepinephrine compared with the canola oil group without salt and to the WKY rats. These results indicate that ingestion of canola oil increases O2 - generation, and that canola oil ingestion in combination with salt leads to endothelial dysfunction in the SHRSP model. © 2013 Papazzo et al.
- Description: 2003011096
Secondary stroke prevention in polish adults: Results from the lipidogram2015 study
- Labuz-Roszak, Beata, Banach, Maciej, Skrzypek, Michal, Windak, Adam, Charchar, Fadi
- Authors: Labuz-Roszak, Beata , Banach, Maciej , Skrzypek, Michal , Windak, Adam , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Journal of Clinical Medicine Vol. 10, no. 19 (2021), p.
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- Description: Background: The purpose of the study was to evaluate secondary stroke prevention in Poland and its association with sociodemographic factors, place of residence, and concomitant cardiovascular risk factors. Material and methods: From all patients in LIPIDOGRAM2015 Study (n = 13,724), 268 subjects had a history of ischaemic stroke and were included. Results: 165 subjects (61.6%) used at least one preventive medication. Oral antiplatelet and anticoagulation agents were used by 116 (43.3%) and 70 (26.1%) patients, respectively. Only 157 (58.6%) participants used lipid-lowering drugs, and 205 (76.5%) were treated with antihypertensive drugs. Coronary heart disease (CHD) and dyslipidaemia were associated with antiplatelet treatment (p = 0.047 and p = 0.012, respectively). A history of atrial fibrillation, CHD, and previous myocardial infarction correlated with anticoagulant treatment (p = 0.001, p = 0.011, and p < 0.0001, respectively). Age, gender, time from stroke onset, place of residence, and level of education were not associated with antiplatelet or anticoagulant treatment. Only 31.7% of patients were engaged in regular physical activity, 62% used appropriate diet, and 13.6% were current smokers. Conclusions: In Poland drugs and lifestyle modification for secondary stroke prevention are not commonly adhered to. Educational programmes for physicians and patients should be developed to improve application of effective secondary prevention of stroke. © 2021 by the authors. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Fadi Charchar” is provided in this record**
- Authors: Labuz-Roszak, Beata , Banach, Maciej , Skrzypek, Michal , Windak, Adam , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Journal of Clinical Medicine Vol. 10, no. 19 (2021), p.
- Full Text:
- Reviewed:
- Description: Background: The purpose of the study was to evaluate secondary stroke prevention in Poland and its association with sociodemographic factors, place of residence, and concomitant cardiovascular risk factors. Material and methods: From all patients in LIPIDOGRAM2015 Study (n = 13,724), 268 subjects had a history of ischaemic stroke and were included. Results: 165 subjects (61.6%) used at least one preventive medication. Oral antiplatelet and anticoagulation agents were used by 116 (43.3%) and 70 (26.1%) patients, respectively. Only 157 (58.6%) participants used lipid-lowering drugs, and 205 (76.5%) were treated with antihypertensive drugs. Coronary heart disease (CHD) and dyslipidaemia were associated with antiplatelet treatment (p = 0.047 and p = 0.012, respectively). A history of atrial fibrillation, CHD, and previous myocardial infarction correlated with anticoagulant treatment (p = 0.001, p = 0.011, and p < 0.0001, respectively). Age, gender, time from stroke onset, place of residence, and level of education were not associated with antiplatelet or anticoagulant treatment. Only 31.7% of patients were engaged in regular physical activity, 62% used appropriate diet, and 13.6% were current smokers. Conclusions: In Poland drugs and lifestyle modification for secondary stroke prevention are not commonly adhered to. Educational programmes for physicians and patients should be developed to improve application of effective secondary prevention of stroke. © 2021 by the authors. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Fadi Charchar” is provided in this record**
Serum antinuclear autoantibodies are associated with measures of oxidative stress and lifestyle factors : analysis of LIPIDOGRAM2015 and LIPIDOGEN2015 studies
- Krzemień, Pawel, Kasperczyk, S, Banach, Maciej, Kasperczyk, Aleksandra, Dobrakowski, Michal, Tomasik, Tomasz, Windak, Adam, Mastej, Miroslaw, Catapano, Alberico, Ray, Kausik, Mikhailidis, Dimitri, Toth, Peter, Howard, George, Lip, Gregory, Tomaszewski, Maciej, Charchar, Fadi, Sattar, Naveed, Williams, Bryan, MacDonald, Thomas, Penson, Peter, Jóźwiak, Jacek
- Authors: Krzemień, Pawel , Kasperczyk, S , Banach, Maciej , Kasperczyk, Aleksandra , Dobrakowski, Michal , Tomasik, Tomasz , Windak, Adam , Mastej, Miroslaw , Catapano, Alberico , Ray, Kausik , Mikhailidis, Dimitri , Toth, Peter , Howard, George , Lip, Gregory , Tomaszewski, Maciej , Charchar, Fadi , Sattar, Naveed , Williams, Bryan , MacDonald, Thomas , Penson, Peter , Jóźwiak, Jacek
- Date: 2023
- Type: Text , Journal article
- Relation: Archives of Medical Science Vol. 19, no. 5 (2023), p. 1214-1227
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- Description: Introduction: Oxidative stress is one of many factors suspected to promote antinuclear autoantibody (ANA) formation. Reactive oxygen species can induce changes in the antigenic structure of macromolecules, causing the immune system to treat them as “neo-antigens” and start production of autoantibodies. This study was designed to evaluate the relationship between oxidative stress markers, lifestyle factors and the detection of ANA. Material and methods: We examined measures of oxidative stress indices of free-radical damage to lipids and proteins, such as total oxidant status (TOS), concentration of protein thiol groups (PSH), and malondialdehyde (MDA), activity of superoxide dismutase (SOD) in 1731 serum samples. The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid (UA) concentration, were also measured and the oxidative stress index (OSI-index) was calculated. All samples were tested for the presence of ANA using an indirect immunofluorescence assay (IIFA). Results: The presence of ANA in women was associated with lower physical activity (p = 0.036), less frequent smoking (p = 0.007) and drinking of alcohol (p = 0.024) accompanied by significant changes in SOD isoenzymes activity (p < 0.001) and a higher uric acid (UA) concentration (p < 0.001). In ANA positive males we observed lower concentrations of PSH (p = 0.046) and increased concentrations of MDA (p = 0.047). Conclusions: The results indicate that local oxidative stress may be associated with increased probability of ANA formation in a sex-specific manner. © 2021 Termedia & Banach.
- Authors: Krzemień, Pawel , Kasperczyk, S , Banach, Maciej , Kasperczyk, Aleksandra , Dobrakowski, Michal , Tomasik, Tomasz , Windak, Adam , Mastej, Miroslaw , Catapano, Alberico , Ray, Kausik , Mikhailidis, Dimitri , Toth, Peter , Howard, George , Lip, Gregory , Tomaszewski, Maciej , Charchar, Fadi , Sattar, Naveed , Williams, Bryan , MacDonald, Thomas , Penson, Peter , Jóźwiak, Jacek
- Date: 2023
- Type: Text , Journal article
- Relation: Archives of Medical Science Vol. 19, no. 5 (2023), p. 1214-1227
- Full Text:
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- Description: Introduction: Oxidative stress is one of many factors suspected to promote antinuclear autoantibody (ANA) formation. Reactive oxygen species can induce changes in the antigenic structure of macromolecules, causing the immune system to treat them as “neo-antigens” and start production of autoantibodies. This study was designed to evaluate the relationship between oxidative stress markers, lifestyle factors and the detection of ANA. Material and methods: We examined measures of oxidative stress indices of free-radical damage to lipids and proteins, such as total oxidant status (TOS), concentration of protein thiol groups (PSH), and malondialdehyde (MDA), activity of superoxide dismutase (SOD) in 1731 serum samples. The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid (UA) concentration, were also measured and the oxidative stress index (OSI-index) was calculated. All samples were tested for the presence of ANA using an indirect immunofluorescence assay (IIFA). Results: The presence of ANA in women was associated with lower physical activity (p = 0.036), less frequent smoking (p = 0.007) and drinking of alcohol (p = 0.024) accompanied by significant changes in SOD isoenzymes activity (p < 0.001) and a higher uric acid (UA) concentration (p < 0.001). In ANA positive males we observed lower concentrations of PSH (p = 0.046) and increased concentrations of MDA (p = 0.047). Conclusions: The results indicate that local oxidative stress may be associated with increased probability of ANA formation in a sex-specific manner. © 2021 Termedia & Banach.
Small molecules, big effects: The role of microRNAs in regulation of cardiomyocyte death
- Skommer, Joanna, Rana, Indrajeetsinh, Marques, Francine, Zhu, Wenliang, Du, Zhimin, Charchar, Fadi
- Authors: Skommer, Joanna , Rana, Indrajeetsinh , Marques, Francine , Zhu, Wenliang , Du, Zhimin , Charchar, Fadi
- Date: 2014
- Type: Text , Journal article
- Relation: Cell Death and Disease Vol. 5, no. 7 (2014), p. e1325
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- Description: MicroRNAs (miRNAs) are a class of small non-coding RNAs involved in posttranscriptional regulation of gene expression, and exerting regulatory roles in plethora of biological processes. In recent years, miRNAs have received increased attention for their crucial role in health and disease, including in cardiovascular disease. This review summarizes the role of miRNAs in regulation of cardiac cell death/cell survival pathways, including apoptosis, autophagy and necrosis. It is envisaged that these miRNAs may explain the mechanisms behind the pathogenesis of many cardiac diseases, and, most importantly, may provide new avenues for therapeutic intervention that will limit cardiomyocyte cell death before it irreversibly affects cardiac function. Through an indepth literature analysis coupled with integrative bioinformatics (pathway and synergy analysis), we dissect here the landscape of complex relationships between the apoptosis-regulating miRNAs in the context of cardiomyocyte cell death (including regulation of autophagy-apoptosis cross talk), and examine the gaps in our current understanding that will guide future investigations.
- Description: C1
- Authors: Skommer, Joanna , Rana, Indrajeetsinh , Marques, Francine , Zhu, Wenliang , Du, Zhimin , Charchar, Fadi
- Date: 2014
- Type: Text , Journal article
- Relation: Cell Death and Disease Vol. 5, no. 7 (2014), p. e1325
- Full Text:
- Reviewed:
- Description: MicroRNAs (miRNAs) are a class of small non-coding RNAs involved in posttranscriptional regulation of gene expression, and exerting regulatory roles in plethora of biological processes. In recent years, miRNAs have received increased attention for their crucial role in health and disease, including in cardiovascular disease. This review summarizes the role of miRNAs in regulation of cardiac cell death/cell survival pathways, including apoptosis, autophagy and necrosis. It is envisaged that these miRNAs may explain the mechanisms behind the pathogenesis of many cardiac diseases, and, most importantly, may provide new avenues for therapeutic intervention that will limit cardiomyocyte cell death before it irreversibly affects cardiac function. Through an indepth literature analysis coupled with integrative bioinformatics (pathway and synergy analysis), we dissect here the landscape of complex relationships between the apoptosis-regulating miRNAs in the context of cardiomyocyte cell death (including regulation of autophagy-apoptosis cross talk), and examine the gaps in our current understanding that will guide future investigations.
- Description: C1
Telomere dynamics during aging in polygenic left ventricular hypertrophy
- Marques, Francine, Booth, Scott, Prestes, Priscilla, Curl, Claire, Delbridge, Lea, Lewandowski, Paul, Harrap, Stephen, Charchar, Fadi
- Authors: Marques, Francine , Booth, Scott , Prestes, Priscilla , Curl, Claire , Delbridge, Lea , Lewandowski, Paul , Harrap, Stephen , Charchar, Fadi
- Date: 2016
- Type: Text , Journal article
- Relation: Physiological Genomics Vol. 48, no. 1 (2016), p. 42-49
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- Description: Short telomeres are associated with increased risk of cardiovascular disease. Here we studied cardiomyocyte telomere length at key ages during the ontogeny of cardiac hypertrophy and failure in the hypertrophic heart rat (HHR) and compared these with the normal heart rat (NHR) control strain. Key ages corresponded with the pathophysiological sequence beginning with fewer cardiomyocytes (2 days), leading to left ventricular hypertrophy (LVH) (13 wk) and subsequently progression to heart failure (38 wk). We measured telomere length, tissue activity of telomerase, mRNA levels of telomerase reverse transcriptase (Tert) and telomerase RNA component (Terc), and expression of the telomeric regulator microRNA miR-34a. Cardiac telomere length was longer in the HHR compared with the control strain at 2 days and 38 wk, but shorter at 13 wk. Neonatal HHR had higher cardiac telomerase activity and expression of Tert and miR-34a. Telomerase activity was not different at 13 or 38 wk. Tert mRNA and Terc RNA were overexpressed at 38 wk, while miR-34a was overexpressed at 13 wk but downregulated at 38 wk. Circulating leukocytes were strongly correlated with cardiac telomere length in the HHR only. The longer neonatal telomeres in HHR are likely to reflect fewer fetal and early postnatal cardiomyocyte cell divisions and explain the reduced total cardiomyocyte complement that predisposes to later hypertrophy and failure. Although shorter telomeres were a feature of cardiac hypertrophy at 13 wk, they were not present at the progression to heart failure at 38 wk. © 2016 the American Physiological Society.
- Authors: Marques, Francine , Booth, Scott , Prestes, Priscilla , Curl, Claire , Delbridge, Lea , Lewandowski, Paul , Harrap, Stephen , Charchar, Fadi
- Date: 2016
- Type: Text , Journal article
- Relation: Physiological Genomics Vol. 48, no. 1 (2016), p. 42-49
- Full Text:
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- Description: Short telomeres are associated with increased risk of cardiovascular disease. Here we studied cardiomyocyte telomere length at key ages during the ontogeny of cardiac hypertrophy and failure in the hypertrophic heart rat (HHR) and compared these with the normal heart rat (NHR) control strain. Key ages corresponded with the pathophysiological sequence beginning with fewer cardiomyocytes (2 days), leading to left ventricular hypertrophy (LVH) (13 wk) and subsequently progression to heart failure (38 wk). We measured telomere length, tissue activity of telomerase, mRNA levels of telomerase reverse transcriptase (Tert) and telomerase RNA component (Terc), and expression of the telomeric regulator microRNA miR-34a. Cardiac telomere length was longer in the HHR compared with the control strain at 2 days and 38 wk, but shorter at 13 wk. Neonatal HHR had higher cardiac telomerase activity and expression of Tert and miR-34a. Telomerase activity was not different at 13 or 38 wk. Tert mRNA and Terc RNA were overexpressed at 38 wk, while miR-34a was overexpressed at 13 wk but downregulated at 38 wk. Circulating leukocytes were strongly correlated with cardiac telomere length in the HHR only. The longer neonatal telomeres in HHR are likely to reflect fewer fetal and early postnatal cardiomyocyte cell divisions and explain the reduced total cardiomyocyte complement that predisposes to later hypertrophy and failure. Although shorter telomeres were a feature of cardiac hypertrophy at 13 wk, they were not present at the progression to heart failure at 38 wk. © 2016 the American Physiological Society.
Telomere length maintenance and cardio-metabolic disease prevention through exercise training
- Denham, Joshua, O'Brien, Brendan, Charchar, Fadi
- Authors: Denham, Joshua , O'Brien, Brendan , Charchar, Fadi
- Date: 2016
- Type: Text , Journal article , Review
- Relation: Sports Medicine Vol. 46, no. 9 (2016), p. 1213-1237
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
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- Description: Telomeres are tandem repeat DNA sequences located at distal ends of chromosomes that protect against genomic DNA degradation and chromosomal instability. Excessive telomere shortening leads to cellular senescence and for this reason telomere length is a marker of biological age. Abnormally short telomeres may culminate in the manifestation of a number of cardio-metabolic diseases. Age-related cardio-metabolic diseases attributable to an inactive lifestyle, such as obesity, type 2 diabetes mellitus and cardiovascular disease, are associated with short leukocyte telomeres. Exercise training prevents and manages the symptoms of many cardio-metabolic diseases whilst concurrently maintaining telomere length. The positive relationship between exercise training, physical fitness and telomere length raises the possibility of a mediating role of telomeres in chronic disease prevention via exercise. Further elucidation of the underpinning molecular mechanisms of how exercise maintains telomere length should provide crucial information on how physical activity can be best structured to combat the chronic disease epidemic and improve the human health span. Here, we synthesise and discuss the current evidence on the impact of physical activity and cardiorespiratory fitness on telomere dynamics. We provide the molecular mechanisms with a known role in exercise-induced telomere length maintenance and highlight unexplored, alternative pathways ripe for future investigations.
- Authors: Denham, Joshua , O'Brien, Brendan , Charchar, Fadi
- Date: 2016
- Type: Text , Journal article , Review
- Relation: Sports Medicine Vol. 46, no. 9 (2016), p. 1213-1237
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
- Reviewed:
- Description: Telomeres are tandem repeat DNA sequences located at distal ends of chromosomes that protect against genomic DNA degradation and chromosomal instability. Excessive telomere shortening leads to cellular senescence and for this reason telomere length is a marker of biological age. Abnormally short telomeres may culminate in the manifestation of a number of cardio-metabolic diseases. Age-related cardio-metabolic diseases attributable to an inactive lifestyle, such as obesity, type 2 diabetes mellitus and cardiovascular disease, are associated with short leukocyte telomeres. Exercise training prevents and manages the symptoms of many cardio-metabolic diseases whilst concurrently maintaining telomere length. The positive relationship between exercise training, physical fitness and telomere length raises the possibility of a mediating role of telomeres in chronic disease prevention via exercise. Further elucidation of the underpinning molecular mechanisms of how exercise maintains telomere length should provide crucial information on how physical activity can be best structured to combat the chronic disease epidemic and improve the human health span. Here, we synthesise and discuss the current evidence on the impact of physical activity and cardiorespiratory fitness on telomere dynamics. We provide the molecular mechanisms with a known role in exercise-induced telomere length maintenance and highlight unexplored, alternative pathways ripe for future investigations.
Telomeres, aging and exercise : Guilty by association?
- Chilton, Warrick, O’Brien, Brendan, Charchar, Fadi
- Authors: Chilton, Warrick , O’Brien, Brendan , Charchar, Fadi
- Date: 2017
- Type: Text , Journal article , Review
- Relation: International Journal of Molecular Sciences Vol. 18, no. 12 (2017), p. 1-32
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- Description: Telomeres are repetitive tandem DNA sequences that cap chromosomal ends protecting genomic DNA from enzymatic degradation. Telomeres progressively shorten with cellular replication and are therefore assumed to correlate with biological and chronological age. An expanding body of evidence suggests (i) a predictable inverse association between telomere length, aging and age-related diseases and (ii) a positive association between physical activity and telomere length. Both hypotheses have garnered tremendous research attention and broad consensus; however, the evidence for each proposition is inconsistent and equivocal at best. Telomere length does not meet the basic criteria for an aging biomarker and at least 50% of key studies fail to find associations with physical activity. In this review, we address the evidence in support and refutation of the putative associations between telomere length, aging and physical activity. We finish with a brief review of plausible mechanisms and potential future research directions. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.
- Authors: Chilton, Warrick , O’Brien, Brendan , Charchar, Fadi
- Date: 2017
- Type: Text , Journal article , Review
- Relation: International Journal of Molecular Sciences Vol. 18, no. 12 (2017), p. 1-32
- Full Text:
- Reviewed:
- Description: Telomeres are repetitive tandem DNA sequences that cap chromosomal ends protecting genomic DNA from enzymatic degradation. Telomeres progressively shorten with cellular replication and are therefore assumed to correlate with biological and chronological age. An expanding body of evidence suggests (i) a predictable inverse association between telomere length, aging and age-related diseases and (ii) a positive association between physical activity and telomere length. Both hypotheses have garnered tremendous research attention and broad consensus; however, the evidence for each proposition is inconsistent and equivocal at best. Telomere length does not meet the basic criteria for an aging biomarker and at least 50% of key studies fail to find associations with physical activity. In this review, we address the evidence in support and refutation of the putative associations between telomere length, aging and physical activity. We finish with a brief review of plausible mechanisms and potential future research directions. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.