The association between selected molecular biomarkers and ambulatory blood pressure patterns in African chronic kidney disease and hypertensive patients compared with normotensive controls : protocol for a longitudinal study
- Adeoye, Abiodun, Adebayo, Oladimeji, Abiola, Busayo, Iwalokun, Bamidele, Tayo, Bamidele, Charchar, Fadi, Ojo, Akinlolu, Cooper, Richard
- Authors: Adeoye, Abiodun , Adebayo, Oladimeji , Abiola, Busayo , Iwalokun, Bamidele , Tayo, Bamidele , Charchar, Fadi , Ojo, Akinlolu , Cooper, Richard
- Date: 2020
- Type: Text , Journal article
- Relation: JMIR Research Protocols Vol. 9, no. 1 (Jan 2020), p. 8
- Full Text:
- Reviewed:
- Description: Background: Chronic kidney disease (CKD) is a burgeoning epidemic in sub-Saharan Africa. Abnormal blood pressure variations are prevalent in CKD and potentiate the risk of cardiovascular morbidity and mortality. Certain genetic variants (angiotensin II receptor type 1 1166 A>C and angiotensin-converting enzyme insertion and deletion polymorphisms) and biomarkers such as interleukin-6, tumor necrosis factor, soluble (s) E-selectin, homocysteine, and highly sensitive C-reactive protein have been shown to affect blood pressure variability among non-African CKD, hypertensive. and nonhypertensive CKD population. However, the contributions of the pattern, genetic, and environmental determinants of ambulatory blood pressure in African CKD have not been characterized. Understanding these interactions may help to develop interventions to prevent major cardiovascular events among people with CKD. Objective: The overarching objective of this study is to identify, document, and develop approaches to address related phenomic, genetic, and environmental determinants of ambulatory blood pressure patterns in African CKD and non-CKD hypertensive patients compared with normotensive controls. Methods: This is a longitudinal short-term follow-up study of 200 adult subjects with CKD and 200 each of age-matched hypertensives without CKD and apparently healthy controls. Demographic information, detailed clinical profile, electrocardiography, echocardiography, and 24-hr ambulatory blood pressure measurements will be obtained. Blood samples will be collected to determine albumin-creatinine ratio, fasting plasma glucose, lipid profile, electrolytes, urea and creatinine, C-reactive protein, serum homocysteine, fibroblast growth factor-23, and complete blood count, while 2 mL blood aliquot will be collected in EDTA (ethylenediaminetetraacetic acid) tubes and mixed using an electronic rolling system to prevent blood clots and subsequently used for DNA extraction and genetic analysis. Results: A total of 239 participants have been recruited so far, and it is expected that the recruitment phase will be complete in June 2020. The follow-up phase will continue with data analysis and publications of results. Conclusions: This study will help stratify Nigerian CKD patients phenotypically and genotypically in terms of their blood pressure variations with implications for targeted interventions and timing of medications to improve prognosis.
- Authors: Adeoye, Abiodun , Adebayo, Oladimeji , Abiola, Busayo , Iwalokun, Bamidele , Tayo, Bamidele , Charchar, Fadi , Ojo, Akinlolu , Cooper, Richard
- Date: 2020
- Type: Text , Journal article
- Relation: JMIR Research Protocols Vol. 9, no. 1 (Jan 2020), p. 8
- Full Text:
- Reviewed:
- Description: Background: Chronic kidney disease (CKD) is a burgeoning epidemic in sub-Saharan Africa. Abnormal blood pressure variations are prevalent in CKD and potentiate the risk of cardiovascular morbidity and mortality. Certain genetic variants (angiotensin II receptor type 1 1166 A>C and angiotensin-converting enzyme insertion and deletion polymorphisms) and biomarkers such as interleukin-6, tumor necrosis factor, soluble (s) E-selectin, homocysteine, and highly sensitive C-reactive protein have been shown to affect blood pressure variability among non-African CKD, hypertensive. and nonhypertensive CKD population. However, the contributions of the pattern, genetic, and environmental determinants of ambulatory blood pressure in African CKD have not been characterized. Understanding these interactions may help to develop interventions to prevent major cardiovascular events among people with CKD. Objective: The overarching objective of this study is to identify, document, and develop approaches to address related phenomic, genetic, and environmental determinants of ambulatory blood pressure patterns in African CKD and non-CKD hypertensive patients compared with normotensive controls. Methods: This is a longitudinal short-term follow-up study of 200 adult subjects with CKD and 200 each of age-matched hypertensives without CKD and apparently healthy controls. Demographic information, detailed clinical profile, electrocardiography, echocardiography, and 24-hr ambulatory blood pressure measurements will be obtained. Blood samples will be collected to determine albumin-creatinine ratio, fasting plasma glucose, lipid profile, electrolytes, urea and creatinine, C-reactive protein, serum homocysteine, fibroblast growth factor-23, and complete blood count, while 2 mL blood aliquot will be collected in EDTA (ethylenediaminetetraacetic acid) tubes and mixed using an electronic rolling system to prevent blood clots and subsequently used for DNA extraction and genetic analysis. Results: A total of 239 participants have been recruited so far, and it is expected that the recruitment phase will be complete in June 2020. The follow-up phase will continue with data analysis and publications of results. Conclusions: This study will help stratify Nigerian CKD patients phenotypically and genotypically in terms of their blood pressure variations with implications for targeted interventions and timing of medications to improve prognosis.
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:
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- 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
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- 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.
Male-specific region of the y chromosome and cardiovascular risk phylogenetic analysis and gene expression studies
- Bloomer, Lisa, Nelson, Christopher, Eales, James, Denniff, Matthew, Christofidou, Paraskevi, Debiec, Radoslaw, Moore, Jasbir, Consortium, Cardiogenics, Zukowska-Szczechowska, Ewa, Goodall, Alison, Thompson, John, Samani, Nilesh, Charchar, Fadi, Tomaszewski, Maciej
- Authors: Bloomer, Lisa , Nelson, Christopher , Eales, James , Denniff, Matthew , Christofidou, Paraskevi , Debiec, Radoslaw , Moore, Jasbir , Consortium, Cardiogenics , Zukowska-Szczechowska, Ewa , Goodall, Alison , Thompson, John , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2013
- Type: Text , Journal article
- Relation: Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 33, no. 7 (2013), p. 1722-1727
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
- Reviewed:
- Description: Objective-Haplogroup I of male-specific region of the human Y chromosome is associated with 50% increased risk of coronary artery disease. It is not clear to what extent conventional cardiovascular risk factors and genes of the malespecific region may explain this association. Approach and Results-A total of 1988 biologically unrelated men from 4 white European populations were genotyped using 11 Y chromosome single nucleotide polymorphisms and classified into 13 most common European haplogroups. Approximately 75% to 93% of the haplotypic variation of the Y chromosome in all cohorts was attributable to I, R1a, and R1b1b2 lineages. None of traditional cardiovascular risk factors, including body mass index, blood pressures, lipids, glucose, C-reactive protein, creatinine, and insulin resistance, was associated with haplogroup I of the Y chromosome in the joint inverse variance meta-analysis. Fourteen of 15 ubiquitous single-copy genes of the male-specific region were expressed in human macrophages. When compared with men with other haplogroups, carriers of haplogroup I had 0.61- and 0.64-fold lower expression of ubiquitously transcribed tetratricopeptide repeat, Y-linked gene (UTY) and protein kinase, Y-linked, pseudogene (PRKY) in macrophages (P=0.0001 and P=0.002, respectively). Conclusions-Coronary artery disease predisposing haplogroup I of the Y chromosome is associated with downregulation of UTY and PRKY genes in macrophages but not with conventional cardiovascular risk factors. © 2013 American Heart Association, Inc.
- Description: 2003011132
- Authors: Bloomer, Lisa , Nelson, Christopher , Eales, James , Denniff, Matthew , Christofidou, Paraskevi , Debiec, Radoslaw , Moore, Jasbir , Consortium, Cardiogenics , Zukowska-Szczechowska, Ewa , Goodall, Alison , Thompson, John , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2013
- Type: Text , Journal article
- Relation: Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 33, no. 7 (2013), p. 1722-1727
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
- Reviewed:
- Description: Objective-Haplogroup I of male-specific region of the human Y chromosome is associated with 50% increased risk of coronary artery disease. It is not clear to what extent conventional cardiovascular risk factors and genes of the malespecific region may explain this association. Approach and Results-A total of 1988 biologically unrelated men from 4 white European populations were genotyped using 11 Y chromosome single nucleotide polymorphisms and classified into 13 most common European haplogroups. Approximately 75% to 93% of the haplotypic variation of the Y chromosome in all cohorts was attributable to I, R1a, and R1b1b2 lineages. None of traditional cardiovascular risk factors, including body mass index, blood pressures, lipids, glucose, C-reactive protein, creatinine, and insulin resistance, was associated with haplogroup I of the Y chromosome in the joint inverse variance meta-analysis. Fourteen of 15 ubiquitous single-copy genes of the male-specific region were expressed in human macrophages. When compared with men with other haplogroups, carriers of haplogroup I had 0.61- and 0.64-fold lower expression of ubiquitously transcribed tetratricopeptide repeat, Y-linked gene (UTY) and protein kinase, Y-linked, pseudogene (PRKY) in macrophages (P=0.0001 and P=0.002, respectively). Conclusions-Coronary artery disease predisposing haplogroup I of the Y chromosome is associated with downregulation of UTY and PRKY genes in macrophages but not with conventional cardiovascular risk factors. © 2013 American Heart Association, Inc.
- Description: 2003011132
- Bloomer, Lisa, Nelson, Christopher, Denniff, Matthew, Christofidou, Paraskevi, Debiec, Radoslaw, Thompson, John, Zukowska-Szczechowska, Ewa, Samani, Nilesh, Charchar, Fadi, Tomaszewski, Maciej
- Authors: Bloomer, Lisa , Nelson, Christopher , Denniff, Matthew , Christofidou, Paraskevi , Debiec, Radoslaw , Thompson, John , Zukowska-Szczechowska, Ewa , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2014
- Type: Text , Journal article
- Relation: Atherosclerosis Vol. 233, no. 1 (2014), p. 160-164
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text: false
- Reviewed:
- Description: Objective: Amongst middle-aged men, haplogroup I is associated with approximate to 50% higher risk of coronary artery disease than other paternal lineages of Y chromosome. We hypothesised that carriers of haplogroup I had higher levels of aggression and estrogens and/or lower levels of androgens early in life and thus might be more prone to cardiovascular disease than men with other lineages of Y chromosome. Methods: We reconstructed phylogenetic tree of the Y chromosome in > 1000 young apparently healthy white men from the general population. Each Y chromosome was classified into one of 13 most common European lineages. Androgens (DHEA-S, androstenedione, total testosterone) and their metabolites (total estradiol, estrone) were measured by radioimmunoassays. Information on five dimensions of aggression (total, physical, verbal, anger and hostility) was collected using Buss and Perry questionnaire. Results: Approximately 17% men inherited haplogroup I from their fathers. Carriers of haplogroup I showed lower scores of verbal aggression than men with other haplogroups (beta = -0.72, SE = 0.29, P = 0.012) and when further compared to carriers of most common R1a lineage and other haplogroups (beta = -1.03, SE = 0.34, P = 0.003). However, these associations did not survive a correction for multiple testing. Sex steroids did not show even nominal level of association with haplogroup I. Conclusion: Our data show no overall association between haplogroup I and sex-related phenotypes in young white men. These results also suggest that the previously identified association between haplogroup I and coronary artery disease is not likely mediated by unfavourable profile of sex steroids or heightened aggression early in life. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
Orthologues of GSTM expressed in human kidney
- Brosnan, Julia, Tomaszewski, Maciej, McBride, Martin, Charchar, Fadi, Lacka, Beata, Zukowska-Szczechowska, Ewa, Grzeszczak, Wladyslaw, Lee, Wai, Dominiczak, Anna
- Authors: Brosnan, Julia , Tomaszewski, Maciej , McBride, Martin , Charchar, Fadi , Lacka, Beata , Zukowska-Szczechowska, Ewa , Grzeszczak, Wladyslaw , Lee, Wai , Dominiczak, Anna
- Date: 2004
- Type: Text , Journal article
- Relation: Journal of Hypertension Vol. 22, no. Suppl. 1 (2004), p. S183
- Full Text: false
- Reviewed:
Report of the 3rd annual International Society of Hypertension New Investigator Symposium.
- Burger, Dylan, Veerabhadrappa, Praveen, Charchar, Fadi, Schutte, Aletta, Tomaszewski, Maciej
- Authors: Burger, Dylan , Veerabhadrappa, Praveen , Charchar, Fadi , Schutte, Aletta , Tomaszewski, Maciej
- Date: 2014
- Type: Text , Journal article
- Relation: Journal of hypertension Vol. 32, no. 4 (2014), p. 448-449
- Full Text: false
- Reviewed:
Whole genome survey of copy number variation in the spontaneously hypertensive rat
- Charchar, Fadi, Samani, Nilesh
- Authors: Charchar, Fadi , Samani, Nilesh
- Date: 2008
- Type: Text , Journal article
- Relation: Hypertension Vol. 52, no. 4 (Oct 2008), p. E100-E100
- Full Text: false
- Reviewed:
- Description: C1
- Charchar, Fadi, Kaiser, Michael, Bingham, Andrew, Fotinatos, Nina, Ahmady, Fahima, Tomaszewski, Maciej, Samani, Nilesh
- Authors: Charchar, Fadi , Kaiser, Michael , Bingham, Andrew , Fotinatos, Nina , Ahmady, Fahima , Tomaszewski, Maciej , Samani, Nilesh
- Date: 2010
- Type: Text , Journal article
- Relation: Hypertension Vol. 55, no. 5 (2010), p. 1231-1238
- Full Text: false
- Reviewed:
- Description: Copy number variation has emerged recently as an important genetic mechanism leading to phenotypic heterogeneity. The aim of our study was to determine whether copy number variants (CNVs) exist between the spontaneously hypertensive rat (SHR) and its control strain, the Wistar-Kyoto rat, whether these map to quantitative trait loci in the rat and whether CNVs associate with gene expression or blood pressure differences between the 2 strains. We performed a comparative genomic hybridization assay between SHR and Wistar-Kyoto strains using a whole-genome array. In total, 16 CNVs were identified and validated (6 because of a relative loss of copy number in the SHR and 10 because of a relative gain). CNVs were present on rat autosomes 1, 3, 4, 6, 7, 10, 14, and 17 and varied in size from 10.0 kb to 1.6 Mb. Most of these CNVs mapped to chromosomal regions within previously identified quantitative trait loci, including those for blood pressure in the SHR. Transcriptomic experiment! s confirmed differences in the renal expression of several genes (including Ms4a6a, Ndr3, Egln1, Cd36, Sema3a, Ugt2b, and Idi21) located in some of the CNVs between STIR and Wistar-Kyoto rats. In F-2 animals derived from an SHRXWistar-Kyoto cross, we also found a significant increase in blood pressure associated with an increase in copy number in the Egln1 gene. Our findings suggest that, CNVs may play a role in the susceptibility to hypertension and related trails in the SHR. (Hypertension. 2010;55:1231-1238.)
- Chilton, Warrick, Marques, Francine, O'Brien, Brendan, Charchar, Fadi
- Authors: Chilton, Warrick , Marques, Francine , O'Brien, Brendan , Charchar, Fadi
- Date: 2012
- Type: Text , Journal article
- Relation: Journal of Hypertension Vol. 30, no. e-Supplement (September 2012), p. e49
- Full Text: false
- Reviewed:
- Description: Background: Compelling epidemiological data demonstrates that regular physical exercise reduces cardiovascular mortality. Telomeres are specialised DNA structures located at the end of linear chromosomes where they protect them from degradation during DNA replication. Telomerase reverse transcriptase (TERT) expression is essential for telomere length maintenance. Accelerated telomere shortening is associated with increased risk of cardiovascular disease (CVD). Sirtuin 6 (SIRT6) is associated with increased longevity and protection against cardiac hypertrophy. Importantly, SIRT6 maintains genomic stability by specifically associating with telomeric chromatin. We hypothesized that acute cardiorespiratory exercise will affect the immediate expression of TERT and SIRT6. Methods: Twenty four healthy adults (19-39 years old) undertook 30 minutes of continuous treadmill running at 80% of maximal oxygen uptake (VO2max). Blood samples were taken before and immediately after exercise. Total RNA was extracted from white blood cells using TRIzol(R) LS reagent. TERT and SIRT6 mRNA expression were measured by real-time PCR. Results: There was no difference in TERT (P = 0.13) and SIRT6 (P = 0.73) mRNA levels immediately after acute cardiorespiratory exercise. Resting TERT levels, however, were negatively correlated with body mass index (BMI) (P = 0.03), waist to hip ratio (P = 0.01) and diastolic blood pressure (BP) (P = 0.05), while a marginal negative correlation was observed with systolic BP (P = 0.07). Conclusions: The results indicate that intense cardiorespiratory exercise does not result in acute modulation of TERT and SIRT6 mRNA. The negative correlations between BP, BMI, waist to hip ratio and TERT levels may provide a mechanistic insight into the established negative correlations between telomere length, hypertension and obesity.
- Description: C1
121 Telomere attrition is attenuated in ultra-marathon runners
- Denham, Joshua, Nankervis, Scott, Debiec, Radek, Harvey, Jack, Pascoe, Deborah, Marques, Francine, O’Brien, Brendan, Zukowska-Szczechowska, Ewa, Tomaszewski, Maciej, Charchar, Fadi
- Authors: Denham, Joshua , Nankervis, Scott , Debiec, Radek , Harvey, Jack , Pascoe, Deborah , Marques, Francine , O’Brien, Brendan , Zukowska-Szczechowska, Ewa , Tomaszewski, Maciej , Charchar, Fadi
- Date: 2012
- Type: Text , Journal article
- Relation: Journal of Hypertension Vol. 30, no. e-Supplement (September 2012), p. e37
- Full Text: false
- Reviewed:
- Description: Background: Leukocyte telomere length is a marker of biological ageing and its shortening is associated with cardiovascular disease. Engagement in regular moderate-intensity physical activity is a recognised method of cardiovascular disease prevention. However, it is not clear whether repeated exposure to ultra-strenuous physical exercise is beneficial long-term and whether it may attenuate biological ageing. Methods: We compared leukocyte telomere length in context of inflammation and endothelial dysfunction between 67 male ultra-marathon runners and 67 age-, sex- and BMI-matched apparently healthy controls. Genomic DNA was extracted from peripheral blood and leukocyte telomere length was measured by quantitative polymerase chain reaction assays. Adhesion molecules (sICAM-1, sE-selectin) and inflammatory markers (IL-6, C-reactive protein) concentrations were measured in 67 ultra-marathon runners by quantitative sandwich enzyme immunoassay technique, high-sensitive immunoassay and ultra-sensitive double antibody sandwich ELISA, respectively. Results: Adjusted (for age, BMI, blood pressure and lipids) leukocyte telomere length was approximately 13.8% greater in the ultra-marathon runners than in the controls (P<0.001). This translates into approximately 32.9 years difference in age-related telomere length attrition. There was a strong negative linear correlation between sICAM-1 and leukocyte telomere length in the ultra-marathon runners (r=-0.33; P=0.007) and this association retained its statistical significance after adjustment for age, BMI, blood pressure and lipids in multiple regression (P=0.026). Conclusion: Prolonged, intense physical exercise may attenuate cellular ageing possibly through a protective effect on endothelial function.
- Description: C1
A multi-omics glimpse into the biology of arterial stiffness
- Eales, James, Romaine, Simon, Charchar, Fadi, Tomaszewski, Maciej
- Authors: Eales, James , Romaine, Simon , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of Hypertension Vol. 34, no. 1 (2015), p. 32-35
- Full Text: false
- Reviewed:
- Description: It has long been recognized that the structure of arteries throughout the vascular tree is not uniform. Notably, the media of large proximal (central) vessels contains relatively much greater amounts of elastin and elastic lamellae than smaller, more distal (peripheral) arteries; the converse is true of vascular smooth muscle cells. Under physiological conditions, the greater elasticity of central arteries compared with more muscular peripheral arteries allows conversion of the pulsatile nature of ventricular ejection into a relatively steady flow of blood at the distal end of the arterial system, conferring protection from pulsatile energy [1,2]. Furthermore, these differences in impedance can generate partial wave reflections, which arrive in the aorta during diastole, boosting diastolic blood pressure and augmenting coronary perfusion pressure [3].
Human Y Chromosome Exerts Pleiotropic Effects on Susceptibility to Atherosclerosis
- Eales, James, Maan, Akhlaq, Xu, Xiaoguang, Michoel, Tom, Hallast, Pille, Batini, C, Zadik, Daniel, Prestes, Priscilla, Molina, Elsa, Denniff, Matthew, Schroeder, Juliane, Bjorkegren, Johan, Thompson, John, Maffia, Pasquale, Guzik, Tomasz, Keavney, Bernard, Jobling, Mark, Samani, Nilesh, Charchar, Fadi, Tomaszewski, Maciej
- Authors: Eales, James , Maan, Akhlaq , Xu, Xiaoguang , Michoel, Tom , Hallast, Pille , Batini, C , Zadik, Daniel , Prestes, Priscilla , Molina, Elsa , Denniff, Matthew , Schroeder, Juliane , Bjorkegren, Johan , Thompson, John , Maffia, Pasquale , Guzik, Tomasz , Keavney, Bernard , Jobling, Mark , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2019
- Type: Text , Journal article
- Relation: Arteriosclerosis, thrombosis, and vascular biology Vol. 39, no. 11 (2019), p. 2386-2401
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- Description: OBJECTIVE: The male-specific region of the Y chromosome (MSY) remains one of the most unexplored regions of the genome. We sought to examine how the genetic variants of the MSY influence male susceptibility to coronary artery disease (CAD) and atherosclerosis. Approach and Results: Analysis of 129 133 men from UK Biobank revealed that only one of 7 common MSY haplogroups (haplogroup I1) was associated with CAD-carriers of haplogroup I1 had ≈11% increase in risk of CAD when compared with all other haplogroups combined (odds ratio, 1.11; 95% CI, 1.04-1.18; P=6.8×10-4). Targeted MSY sequencing uncovered 235 variants exclusive to this haplogroup. The haplogroup I1-specific variants showed 2.45- and 1.56-fold respective enrichment for promoter and enhancer chromatin states, in cells/tissues relevant to atherosclerosis, when compared with other MSY variants. Gene set enrichment analysis in CAD-relevant tissues showed that haplogroup I1 was associated with changes in pathways responsible for early and late stages of atherosclerosis development including defence against pathogens, immunity, oxidative phosphorylation, mitochondrial respiration, lipids, coagulation, and extracellular matrix remodeling. UTY was the only Y chromosome gene whose blood expression was associated with haplogroup I1. Experimental reduction of UTY expression in macrophages led to changes in expression of 59 pathways (28 of which overlapped with those associated with haplogroup I1) and a significant reduction in the immune costimulatory signal. CONCLUSIONS: Haplogroup I1 is enriched for regulatory chromatin variants in numerous cells of relevance to CAD and increases cardiovascular risk through proatherosclerotic reprogramming of the transcriptome, partly through UTY.
- Authors: Eales, James , Maan, Akhlaq , Xu, Xiaoguang , Michoel, Tom , Hallast, Pille , Batini, C , Zadik, Daniel , Prestes, Priscilla , Molina, Elsa , Denniff, Matthew , Schroeder, Juliane , Bjorkegren, Johan , Thompson, John , Maffia, Pasquale , Guzik, Tomasz , Keavney, Bernard , Jobling, Mark , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2019
- Type: Text , Journal article
- Relation: Arteriosclerosis, thrombosis, and vascular biology Vol. 39, no. 11 (2019), p. 2386-2401
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- Description: OBJECTIVE: The male-specific region of the Y chromosome (MSY) remains one of the most unexplored regions of the genome. We sought to examine how the genetic variants of the MSY influence male susceptibility to coronary artery disease (CAD) and atherosclerosis. Approach and Results: Analysis of 129 133 men from UK Biobank revealed that only one of 7 common MSY haplogroups (haplogroup I1) was associated with CAD-carriers of haplogroup I1 had ≈11% increase in risk of CAD when compared with all other haplogroups combined (odds ratio, 1.11; 95% CI, 1.04-1.18; P=6.8×10-4). Targeted MSY sequencing uncovered 235 variants exclusive to this haplogroup. The haplogroup I1-specific variants showed 2.45- and 1.56-fold respective enrichment for promoter and enhancer chromatin states, in cells/tissues relevant to atherosclerosis, when compared with other MSY variants. Gene set enrichment analysis in CAD-relevant tissues showed that haplogroup I1 was associated with changes in pathways responsible for early and late stages of atherosclerosis development including defence against pathogens, immunity, oxidative phosphorylation, mitochondrial respiration, lipids, coagulation, and extracellular matrix remodeling. UTY was the only Y chromosome gene whose blood expression was associated with haplogroup I1. Experimental reduction of UTY expression in macrophages led to changes in expression of 59 pathways (28 of which overlapped with those associated with haplogroup I1) and a significant reduction in the immune costimulatory signal. CONCLUSIONS: Haplogroup I1 is enriched for regulatory chromatin variants in numerous cells of relevance to CAD and increases cardiovascular risk through proatherosclerotic reprogramming of the transcriptome, partly through UTY.
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
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- 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
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- 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.
- Haitjema, Saskia, van Setten, Jessica, Eales, James, van der Laan, Sander, Gandin, Ilaria, de Vries, Jean-Paul, de Borst, Gert, Pasterkamp, Gerard, Asselbergs, Folkert, Charchar, Fadi, Wilson, James, de Jager, Saskia, Tomaszewski, Maciej, den Ruijter, Hester
- Authors: Haitjema, Saskia , van Setten, Jessica , Eales, James , van der Laan, Sander , Gandin, Ilaria , de Vries, Jean-Paul , de Borst, Gert , Pasterkamp, Gerard , Asselbergs, Folkert , Charchar, Fadi , Wilson, James , de Jager, Saskia , Tomaszewski, Maciej , den Ruijter, Hester
- Date: 2017
- Type: Text , Journal article
- Relation: Atherosclerosis Vol. 259, no. (2017), p. 114-119
- Full Text: false
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- Description: Background and aims: Haplogroup I, a common European paternal lineage of the Y chromosome, is associated with increased risk of coronary artery disease in British men. It is unclear whether this haplogroup or any other haplogroup on the Y chromosome is associated with histological characteristics of the diseased vessel wall in other vascular manifestations of cardiovascular diseases showing a male preponderance. Methods: We examined Dutch men undergoing either carotid endarterectomy from the Athero-Express biobank (AE, n = 1217) or open aneurysm repair from the Aneurysm-Express biobank (AAA, n = 393). Upon resolving the Y chromosome phylogeny, each man was assigned to one of the paternal lineages based on combinations of single nucleotide polymorphisms of the male-specific region of the Y chromosome. We examined the associations between the Y chromosome and the histological characteristics of the carotid plaque and aneurysm wall, including lipid content, leukocyte infiltration and intraplaque haemorrhage, in all men. Results: A majority of men were carriers of either haplogroup I (AE: 28% AAA: 24%) or haplogroup R (AE: 59% AAA: 61%). We found no association between Y chromosomal haplogroups and histological characteristics of plaque collected from carotid arteries or tissue specimens of aneurysms. Moreover, the distribution of frequency for all Y chromosomal haplogroups in both cohorts was similar to that of a general population of Dutch men. Conclusions: Our data show that genetic variation on the Y chromosome is not associated with histological characteristics of the plaques from carotid arteries or specimens of aneurysms in men of Dutch origin. © 2017 Elsevier B.V.
Early treatment to prevent hypertension: A laudable goal
- Harrap, Stephen, Charchar, Fadi
- Authors: Harrap, Stephen , Charchar, Fadi
- Date: 2013
- Type: Text , Journal article
- Relation: American Journal of Hypertension Vol. 26, no. 11 (December 2013 2013), p. 1367-1368
- Full Text: false
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Genetics of blood pressure : Time to curate the collection
- Harrap, Stephen, Charchar, Fadi
- Authors: Harrap, Stephen , Charchar, Fadi
- Date: 2017
- Type: Text , Journal article , Editorial
- Relation: Journal of Hypertension Vol. 35, no. 7 (2017), p. 1360-1362
- Full Text: false
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- Description: The genetics of blood pressure (BP) is all about discovery and understanding, but it is certainly not for the faint hearted. Despite heroic effort, the question we posed nearly 15 years ago [1] regarding the whereabouts of BP genes remains largely unanswered.
- Jackson, Kristy, Gueguen, Cindy, Lim, Kyungjoon, Eikelis, Nina, Stevenson, Emily, Charchar, Fadi, Lambert, Gavin, Burke, Sandra, Paterson, Madeleine, Marques, Francine, Head, Geoffrey
- Authors: Jackson, Kristy , Gueguen, Cindy , Lim, Kyungjoon , Eikelis, Nina , Stevenson, Emily , Charchar, Fadi , Lambert, Gavin , Burke, Sandra , Paterson, Madeleine , Marques, Francine , Head, Geoffrey
- Date: 2020
- Type: Text , Journal article
- Relation: Hypertension Research Vol. 43, no. 11 (2020), p. 1152-1164
- Full Text: false
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- Description: BPH/2J mice are a genetic model of hypertension with overactivity of the sympathetic nervous system (SNS) and renin–angiotensin system (RAS). BPH/2J display higher renal renin mRNA and low levels of its negative regulator microRNA-181a (miR-181a). We hypothesise that high renal SNS activity may reduce miR-181a expression, which contributes to elevated RAS activity and hypertension in BPH/2J. Our aim was to determine whether in vivo administration of a renal-specific miR-181a mimic or whether renal denervation could increase renal miR-181a abundance to reduce renal renin mRNA, RAS activity and hypertension in BPH/2J mice. Blood pressure (BP) in BPH/2J and normotensive BPN/3J mice was measured via radiotelemetry probes. Mice were administered miR-181a mimic or a negative control (1–25 nmol, i.v., n = 6–10) with BP measured for 48 h after each dose or they underwent renal denervation or sham surgery (n = 7–9). Injection of 5–25 nmol miR-181a mimic reduced BP in BPH/2J mice after 36–48 h (−5.3 ± 1.8, −6.1 ± 1.9 mmHg, respectively, P < 0.016). Treatment resulted in lower renal renin and inflammatory marker (TLR4) mRNA levels in BPH/2J. The mimic abolished the hypotensive effect of blocking the RAS with enalaprilat (P < 0.01). No differences between mimic or vehicle were observed in BPN/3J mice except for a higher level of renal angiotensinogen in the mimic-treated mice. Renal miR-181a levels that were lower in sham BPH/2J mice were greater following renal denervation and were thus similar to those of BPN/3J. Our findings suggest that the reduced renal miR-181a may partially contribute to the elevated BP in BPH/2J mice, through an interaction between the renal sympathetic nerves and miR-181a regulation of the RAS. © 2020, The Japanese Society of Hypertension.
- Description: This work was supported by a grant from the National Health & Medical Research Council of Australia (NHMRC, Project grant 1065714) and in part by the Victorian Government’s OIS Program. Investigators were supported by NHMRC/National Heart Foundation (NHF) Postdoctoral Fellowships (NHMRC APP1091688 to KLJ, NHMRC APP1052659 and NHF PF12M6785 and 101185 to FZM) and NHMRC Research Fellowships (APP1042492 to GWL and APP1002186 to GAH).
- Jackson, Kristy, Marques, Francine, Watson, Anna, Palma-Rigo, Keisia, Nguyen-Huu, Thu-Phuc, Morris, Brian, Charchar, Fadi, Davern, Pamela, Head, Geoffrey
- Authors: Jackson, Kristy , Marques, Francine , Watson, Anna , Palma-Rigo, Keisia , Nguyen-Huu, Thu-Phuc , Morris, Brian , Charchar, Fadi , Davern, Pamela , Head, Geoffrey
- Date: 2013
- Type: Text , Journal article
- Relation: Hypertension Vol. 62 , no. 4 (2013), p. 775-781
- Full Text: false
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- Description: Genetically hypertensive mice (BPH/2J) are hypertensive because of an exaggerated contribution of the sympathetic nervous system to blood pressure. We hypothesize that an additional contribution to elevated blood pressure is via sympathetically mediated activation of the intrarenal renin-angiotensin system. Our aim was to determine the contribution of the renin-angiotensin system and sympathetic nervous system to hypertension in BPH/2J mice. BPH/2J and normotensive BPN/3J mice were preimplanted with radiotelemetry devices to measure blood pressure. Depressor responses to ganglion blocker pentolinium (5 mg/kg i.p.) in mice pretreated with the angiotensin-converting enzyme inhibitor enalaprilat (1.5 mg/kg i.p.) revealed a 2-fold greater sympathetic contribution to blood pressure in BPH/2J mice during the active and inactive period. However, the depressor response to enalaprilat was 4-fold greater in BPH/2J compared with BPN/3J mice, but only during the active period (P=0.01). This was associated with 1.6-fold higher renal renin messenger RNA (mRNA; P=0.02) and 0.8-fold lower abundance of micro-RNA-181a (P=0.03), identified previously as regulating human renin mRNA. Renin mRNA levels correlated positively with depressor responses to pentolinium (r=0.99; P=0.001), and BPH/2J mice had greater renal sympathetic innervation density as identified by tyrosine hydroxylase staining of cortical tubules. Although there is a major sympathetic contribution to hypertension in BPH/2J mice, the renin-angiotensin system also contributes, doing so to a greater extent during the active period and less during the inactive period. This is the opposite of the normal renin-angiotensin system circadian pattern. We suggest that renal hyperinnervation and enhanced sympathetically induced renin synthesis mediated by lower micro-RNA-181a contributes to hypertension in BPH/2J mice.
Hypertension and renin-angiotensin system blockers are not associated with expression of angiotensin-converting enzyme 2 (ACE2) in the kidney
- Jiang, Xiao, Eales, James, Scannali, David, Prestes, Priscilla, Charchar, Fadi
- Authors: Jiang, Xiao , Eales, James , Scannali, David , Prestes, Priscilla , Charchar, Fadi
- Date: 2020
- Type: Text , Journal article
- Relation: European Heart Journal Vol. 41, no. 48 (2020), p. 4580-4588
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- Description: Aims Angiotensin-converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2) - the cause of coronavirus disease 2019 (COVID-19). However, the effect of renin-angiotensin system (RAS)-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported. Methods and results We examined how hypertension, its major metabolic co-phenotypes, and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterized by RNA-sequencing. We further validated some of the key observations in other human tissues and/or a controlled experimental model. Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 coexpression analysis. Conclusion Our results indicate that neither hypertension nor antihypertensive treatment is likely to alter the expression of the key entry receptor for SARS-CoV-2 in the human kidney. Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection. © The Author(s) 2020. *Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliates “James Eales", "Priscilla Prestes" and "Fadi Charchar” are provided in this record**
- Authors: Jiang, Xiao , Eales, James , Scannali, David , Prestes, Priscilla , Charchar, Fadi
- Date: 2020
- Type: Text , Journal article
- Relation: European Heart Journal Vol. 41, no. 48 (2020), p. 4580-4588
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- Description: Aims Angiotensin-converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2) - the cause of coronavirus disease 2019 (COVID-19). However, the effect of renin-angiotensin system (RAS)-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported. Methods and results We examined how hypertension, its major metabolic co-phenotypes, and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterized by RNA-sequencing. We further validated some of the key observations in other human tissues and/or a controlled experimental model. Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 coexpression analysis. Conclusion Our results indicate that neither hypertension nor antihypertensive treatment is likely to alter the expression of the key entry receptor for SARS-CoV-2 in the human kidney. Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection. © The Author(s) 2020. *Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliates “James Eales", "Priscilla Prestes" and "Fadi Charchar” are provided in this record**