Lifestyle management of hypertension : International Society of Hypertension position paper endorsed by the World Hypertension League and European Society of Hypertension
- Charchar, Fadi, Prestes, Priscilla, Mills, Charlotte, Ching, Siew, Neupane, Dinesh, Marques, Francine, Sharman, James, Vogt, Liffert, Burrell, Louise, Korostovtseva, Lyudmila, Zec, Manja, Patil, Mansi, Schultz, Martin, Wallen, Matthew, Renna, Nicolás, Islam, Sheikh, Hiremath, Swapnil, Gyeltshen, Tshewang, Chia, Yook-Chin, Gupta, Abhinav, Schutte, Aletta, Klein, Britt, Borghi, Claudio, Browning, Colette, Czesnikiewicz-Guzik, Marta, Lee, Hae-Young, Itoh, Hiroshi, Miura, Katsuyuki, Akinnibosun, Olutope, Shane Thomas
- Authors: Charchar, Fadi , Prestes, Priscilla , Mills, Charlotte , Ching, Siew , Neupane, Dinesh , Marques, Francine , Sharman, James , Vogt, Liffert , Burrell, Louise , Korostovtseva, Lyudmila , Zec, Manja , Patil, Mansi , Schultz, Martin , Wallen, Matthew , Renna, Nicolás , Islam, Sheikh , Hiremath, Swapnil , Gyeltshen, Tshewang , Chia, Yook-Chin , Gupta, Abhinav , Schutte, Aletta , Klein, Britt , Borghi, Claudio , Browning, Colette , Czesnikiewicz-Guzik, Marta , Lee, Hae-Young , Itoh, Hiroshi , Miura, Katsuyuki , Akinnibosun, Olutope , Shane Thomas
- Date: 2024
- Type: Text , Journal article
- Relation: Journal of hypertension Vol. 42, no. 1 (2024), p. 23-49
- Full Text:
- Reviewed:
- Description: Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools. **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliates “Fadi Charchar, Priscilla Prestes, Britt Klein, Colette Browning, Olutope Akinnibosun and Shane Thomas” are provided in this record**
- Description: Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools. **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliates “Fadi Charchar, Priscilla Prestes, Britt Klein, Colette Browning, Olutope Akinnibossun and Shane Thomas” are provided in this record**
- Authors: Charchar, Fadi , Prestes, Priscilla , Mills, Charlotte , Ching, Siew , Neupane, Dinesh , Marques, Francine , Sharman, James , Vogt, Liffert , Burrell, Louise , Korostovtseva, Lyudmila , Zec, Manja , Patil, Mansi , Schultz, Martin , Wallen, Matthew , Renna, Nicolás , Islam, Sheikh , Hiremath, Swapnil , Gyeltshen, Tshewang , Chia, Yook-Chin , Gupta, Abhinav , Schutte, Aletta , Klein, Britt , Borghi, Claudio , Browning, Colette , Czesnikiewicz-Guzik, Marta , Lee, Hae-Young , Itoh, Hiroshi , Miura, Katsuyuki , Akinnibosun, Olutope , Shane Thomas
- Date: 2024
- Type: Text , Journal article
- Relation: Journal of hypertension Vol. 42, no. 1 (2024), p. 23-49
- Full Text:
- Reviewed:
- Description: Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools. **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliates “Fadi Charchar, Priscilla Prestes, Britt Klein, Colette Browning, Olutope Akinnibosun and Shane Thomas” are provided in this record**
- Description: Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools. **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliates “Fadi Charchar, Priscilla Prestes, Britt Klein, Colette Browning, Olutope Akinnibossun and Shane Thomas” are provided in this record**
Addressing global disparities in blood pressure control : perspectives of the International Society of Hypertension
- Schutte, Aletta, Jafar, Tazeen, Poulter, Neil, Damasceno, Albertino, Khan, Nadia, Nilsson, Peter, Alsaid, Jafar, Neupane, Dinesh, Kario, Kazuomi, Beheiry, Hind, Brouwers, Sofie, Burger, Dylan, Charchar, Fadi, Cho, Myeong-Chan, Guzik, Tomasz, Haji Al-Saedi, Ghazi, Ishaq, Muhammad, Itoh, Hiroshi, Jones, Erika, Khan, Taskeen, Kokubo, Yoshihiro, Kotruchin, Praew, Muxfeldt, Elizabeth, Odili, Augustine, Patil, Mansi, Ralapanawa, Udaya, Romero, Cesar, Schlaich, Markus, Shehab, Abdulla, Mooi, Ching
- Authors: Schutte, Aletta , Jafar, Tazeen , Poulter, Neil , Damasceno, Albertino , Khan, Nadia , Nilsson, Peter , Alsaid, Jafar , Neupane, Dinesh , Kario, Kazuomi , Beheiry, Hind , Brouwers, Sofie , Burger, Dylan , Charchar, Fadi , Cho, Myeong-Chan , Guzik, Tomasz , Haji Al-Saedi, Ghazi , Ishaq, Muhammad , Itoh, Hiroshi , Jones, Erika , Khan, Taskeen , Kokubo, Yoshihiro , Kotruchin, Praew , Muxfeldt, Elizabeth , Odili, Augustine , Patil, Mansi , Ralapanawa, Udaya , Romero, Cesar , Schlaich, Markus , Shehab, Abdulla , Mooi, Ching
- Date: 2023
- Type: Text , Journal article , Review
- Relation: Cardiovascular Research Vol. 119, no. 2 (2023), p. 381-409
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- Reviewed:
- Description: Raised blood pressure (BP) is the leading cause of preventable death in the world. Yet, its global prevalence is increasing, and it remains poorly detected, treated, and controlled in both high- and low-resource settings. From the perspective of members of the International Society of Hypertension based in all regions, we reflect on the past, present, and future of hypertension care, highlighting key challenges and opportunities, which are often region-specific. We report that most countries failed to show sufficient improvements in BP control rates over the past three decades, with greater improvements mainly seen in some high-income countries, also reflected in substantial reductions in the burden of cardiovascular disease and deaths. Globally, there are significant inequities and disparities based on resources, sociodemographic environment, and race with subsequent disproportionate hypertension-related outcomes. Additional unique challenges in specific regions include conflict, wars, migration, unemployment, rapid urbanization, extremely limited funding, pollution, COVID-19-related restrictions and inequalities, obesity, and excessive salt and alcohol intake. Immediate action is needed to address suboptimal hypertension care and related disparities on a global scale. We propose a Global Hypertension Care Taskforce including multiple stakeholders and societies to identify and implement actions in reducing inequities, addressing social, commercial, and environmental determinants, and strengthening health systems implement a well-designed customized quality-of-care improvement framework. © 2022 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology. **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: Schutte, Aletta , Jafar, Tazeen , Poulter, Neil , Damasceno, Albertino , Khan, Nadia , Nilsson, Peter , Alsaid, Jafar , Neupane, Dinesh , Kario, Kazuomi , Beheiry, Hind , Brouwers, Sofie , Burger, Dylan , Charchar, Fadi , Cho, Myeong-Chan , Guzik, Tomasz , Haji Al-Saedi, Ghazi , Ishaq, Muhammad , Itoh, Hiroshi , Jones, Erika , Khan, Taskeen , Kokubo, Yoshihiro , Kotruchin, Praew , Muxfeldt, Elizabeth , Odili, Augustine , Patil, Mansi , Ralapanawa, Udaya , Romero, Cesar , Schlaich, Markus , Shehab, Abdulla , Mooi, Ching
- Date: 2023
- Type: Text , Journal article , Review
- Relation: Cardiovascular Research Vol. 119, no. 2 (2023), p. 381-409
- Full Text:
- Reviewed:
- Description: Raised blood pressure (BP) is the leading cause of preventable death in the world. Yet, its global prevalence is increasing, and it remains poorly detected, treated, and controlled in both high- and low-resource settings. From the perspective of members of the International Society of Hypertension based in all regions, we reflect on the past, present, and future of hypertension care, highlighting key challenges and opportunities, which are often region-specific. We report that most countries failed to show sufficient improvements in BP control rates over the past three decades, with greater improvements mainly seen in some high-income countries, also reflected in substantial reductions in the burden of cardiovascular disease and deaths. Globally, there are significant inequities and disparities based on resources, sociodemographic environment, and race with subsequent disproportionate hypertension-related outcomes. Additional unique challenges in specific regions include conflict, wars, migration, unemployment, rapid urbanization, extremely limited funding, pollution, COVID-19-related restrictions and inequalities, obesity, and excessive salt and alcohol intake. Immediate action is needed to address suboptimal hypertension care and related disparities on a global scale. We propose a Global Hypertension Care Taskforce including multiple stakeholders and societies to identify and implement actions in reducing inequities, addressing social, commercial, and environmental determinants, and strengthening health systems implement a well-designed customized quality-of-care improvement framework. © 2022 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology. **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**
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.
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- 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
A guide to the short, long and circular RNAs in hypertension and cardiovascular disease
- Prestes, Priscilla, Maier, Michelle, Woods, Bradley, Charchar, Fadi
- Authors: Prestes, Priscilla , Maier, Michelle , Woods, Bradley , Charchar, Fadi
- Date: 2020
- Type: Text , Journal article , Review
- Relation: International Journal of Molecular Sciences Vol. 21, no. 10 (2020)
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- Reviewed:
- Description: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in adults in developed countries. CVD encompasses many diseased states, including hypertension, coronary artery disease and atherosclerosis. Studies in animal models and human studies have elucidated the contribution of many genetic factors, including non-coding RNAs. Non-coding RNAs are RNAs not translated into protein, involved in gene expression regulation post-transcriptionally and implicated in CVD. Of these, circular RNAs (circRNAs) and microRNAs are relevant. CircRNAs are created by the back-splicing of pre-messenger RNA and have been underexplored as contributors to CVD. These circRNAs may also act as biomarkers of human disease, as they can be extracted from whole blood, plasma, saliva and seminal fluid. CircRNAs have recently been implicated in various disease processes, including hypertension and other cardiovascular disease. This review article will explore the promising and emerging roles of circRNAs as potential biomarkers and therapeutic targets in CVD, in particular hypertension. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
- Authors: Prestes, Priscilla , Maier, Michelle , Woods, Bradley , Charchar, Fadi
- Date: 2020
- Type: Text , Journal article , Review
- Relation: International Journal of Molecular Sciences Vol. 21, no. 10 (2020)
- Full Text:
- Reviewed:
- Description: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in adults in developed countries. CVD encompasses many diseased states, including hypertension, coronary artery disease and atherosclerosis. Studies in animal models and human studies have elucidated the contribution of many genetic factors, including non-coding RNAs. Non-coding RNAs are RNAs not translated into protein, involved in gene expression regulation post-transcriptionally and implicated in CVD. Of these, circular RNAs (circRNAs) and microRNAs are relevant. CircRNAs are created by the back-splicing of pre-messenger RNA and have been underexplored as contributors to CVD. These circRNAs may also act as biomarkers of human disease, as they can be extracted from whole blood, plasma, saliva and seminal fluid. CircRNAs have recently been implicated in various disease processes, including hypertension and other cardiovascular disease. This review article will explore the promising and emerging roles of circRNAs as potential biomarkers and therapeutic targets in CVD, in particular hypertension. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- Surendran, Praveen, Feofanova, Elena, Lahrouchi, Najim, Ntalla, Ionna, Karthikeyan, Savita, Cook, James, Chen, Lingyan, Mifsud, Borbala, Yao, Chen, Kraja, Aldi, Cartwright, James, Hellwege, Jacklyn, Giri, Ayush, Tragante, Vinicius, Thorleifsson, Gudmar, Liu, Dajiang, Prins, Bram, Stewart, Isobel, Cabrera, Claude, Eales, James, Akbarov, Artur, Auer, Paul, Charchar, Fadi, Howson, Joanna, LifeLines Cohort, Study, Epic, C. V. D., Epic InterAct, Understanding Society Scientific, Group, Million Veteran, Program
- Authors: Surendran, Praveen , Feofanova, Elena , Lahrouchi, Najim , Ntalla, Ionna , Karthikeyan, Savita , Cook, James , Chen, Lingyan , Mifsud, Borbala , Yao, Chen , Kraja, Aldi , Cartwright, James , Hellwege, Jacklyn , Giri, Ayush , Tragante, Vinicius , Thorleifsson, Gudmar , Liu, Dajiang , Prins, Bram , Stewart, Isobel , Cabrera, Claude , Eales, James , Akbarov, Artur , Auer, Paul , Charchar, Fadi , Howson, Joanna , LifeLines Cohort, Study , Epic, C. V. D. , Epic InterAct , Understanding Society Scientific, Group , Million Veteran, Program
- Date: 2020
- Type: Text , Journal article
- Relation: Nature Genetics Vol. 52, no. 12 (2020), p. 1314-1332
- Full Text:
- Reviewed:
- Description: Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10−8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. There are 286 authors of this articles not all are listed in this record.
- Authors: Surendran, Praveen , Feofanova, Elena , Lahrouchi, Najim , Ntalla, Ionna , Karthikeyan, Savita , Cook, James , Chen, Lingyan , Mifsud, Borbala , Yao, Chen , Kraja, Aldi , Cartwright, James , Hellwege, Jacklyn , Giri, Ayush , Tragante, Vinicius , Thorleifsson, Gudmar , Liu, Dajiang , Prins, Bram , Stewart, Isobel , Cabrera, Claude , Eales, James , Akbarov, Artur , Auer, Paul , Charchar, Fadi , Howson, Joanna , LifeLines Cohort, Study , Epic, C. V. D. , Epic InterAct , Understanding Society Scientific, Group , Million Veteran, Program
- Date: 2020
- Type: Text , Journal article
- Relation: Nature Genetics Vol. 52, no. 12 (2020), p. 1314-1332
- Full Text:
- Reviewed:
- Description: Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10−8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. There are 286 authors of this articles not all are listed in this record.
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
- Full Text:
- Reviewed:
- 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**
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.
- 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
- Reviewed:
- 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).
The prevalence of cardiovascular risk factors and cardiovascular disease among primary care patients in Poland : results from the LIPIDOGRAM2015 study
- Jóźwiak, Jacek, Studziński, Krzysztof, Tomasik, Tomasz, Windak, Adam, Charchar, Fadi
- Authors: Jóźwiak, Jacek , Studziński, Krzysztof , Tomasik, Tomasz , Windak, Adam , Charchar, Fadi
- Date: 2020
- Type: Text , Journal article
- Relation: Atherosclerosis Supplements Vol. 42, no. (2020), p. e15-e24
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- Reviewed:
- Description: Background and aim: To estimate the prevalence of cardiovascular (CV) disease and CV risk factors among Polish patients. Methods: A nationwide cross-sectional study, LIPIDOGRAM2015, was carried out in Poland in the 4th quarter of 2015 and 1st and 2nd quarters of 2016; 438 primary care physicians enrolled 13,724 adult patients that sought medical care in primary health care practices. Results: Nearly 19% of men and approximately 12% of women had cardiovascular disease (CVD). Over 60% of the recruited patients had hypertension (HTN), >80% had dyslipidaemia and <15% of patients were diagnosed with diabetes (DM). All of these disorders were more frequent in men. In 80% of patients the waist circumference exceed norm for the European population. Less than half of the patients were current smokers or had smoked in the past. Patients with CVD had significantly higher blood pressure and glucose levels but lower low density lipoprotein-cholesterol level. Conclusions: The prevalence of CVD and CV risk factors among patients in Poland is high. CVD is more common in men than in women. The most common CV risk factors are excess waist circumference, dyslipidaemia and HTN. Family physicians should conduct activities to prevent, diagnose early and treat CVD in the primary health care population. © 2021 Elsevier B.V. **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: Jóźwiak, Jacek , Studziński, Krzysztof , Tomasik, Tomasz , Windak, Adam , Charchar, Fadi
- Date: 2020
- Type: Text , Journal article
- Relation: Atherosclerosis Supplements Vol. 42, no. (2020), p. e15-e24
- Full Text:
- Reviewed:
- Description: Background and aim: To estimate the prevalence of cardiovascular (CV) disease and CV risk factors among Polish patients. Methods: A nationwide cross-sectional study, LIPIDOGRAM2015, was carried out in Poland in the 4th quarter of 2015 and 1st and 2nd quarters of 2016; 438 primary care physicians enrolled 13,724 adult patients that sought medical care in primary health care practices. Results: Nearly 19% of men and approximately 12% of women had cardiovascular disease (CVD). Over 60% of the recruited patients had hypertension (HTN), >80% had dyslipidaemia and <15% of patients were diagnosed with diabetes (DM). All of these disorders were more frequent in men. In 80% of patients the waist circumference exceed norm for the European population. Less than half of the patients were current smokers or had smoked in the past. Patients with CVD had significantly higher blood pressure and glucose levels but lower low density lipoprotein-cholesterol level. Conclusions: The prevalence of CVD and CV risk factors among patients in Poland is high. CVD is more common in men than in women. The most common CV risk factors are excess waist circumference, dyslipidaemia and HTN. Family physicians should conduct activities to prevent, diagnose early and treat CVD in the primary health care population. © 2021 Elsevier B.V. **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**
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.
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.
May measurement month 2017 : an analysis of blood pressure screening results worldwide
- Beaney, Thomas, Schutte, Aletta, Tomaszewski, Maciej, Ariti, Cono, Burrell, Louise, Castillo, Rafael, Charchar, Fadi, Damasceno, Albertino, Kruger, Ruan, Lackland, Daniel, Nilsson, Peter, Prabhakaran, Dorairaj, Ramirez, Agustin, Schlaich, Markus, Wang, Jiguang, Weber, Michael, Poulter, Neil
- Authors: Beaney, Thomas , Schutte, Aletta , Tomaszewski, Maciej , Ariti, Cono , Burrell, Louise , Castillo, Rafael , Charchar, Fadi , Damasceno, Albertino , Kruger, Ruan , Lackland, Daniel , Nilsson, Peter , Prabhakaran, Dorairaj , Ramirez, Agustin , Schlaich, Markus , Wang, Jiguang , Weber, Michael , Poulter, Neil
- Date: 2018
- Type: Text , Journal article
- Relation: The Lancet Global Health Vol. 6, no. 7 (2018), p. e736-e743
- Full Text:
- Reviewed:
- Description: Background: Increased blood pressure is the biggest contributor to the global burden of disease and mortality. Data suggest that less than half of the population with hypertension is aware of it. May Measurement Month was initiated to raise awareness of the importance of blood pressure and as a pragmatic interim solution to the shortfall in screening programmes. Methods: This cross-sectional survey included volunteer adults (≥18 years) who ideally had not had their blood pressures measured in the past year. Each participant had their blood pressure measured three times and received a a questionnaire about demographic, lifestyle, and environmental factors. The primary objective was to raise awareness of blood pressure, measured by number of countries involved, number of people screened, and number of people who have untreated or inadequately treated hypertension (defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or both, or on the basis of receiving antihypertensive medication). Multiple imputation was used to estimate the mean of the second and third blood pressure readings if these were not recorded. Measures of association were analysed using linear mixed models. Findings: Data were collected from 1 201 570 individuals in 80 countries. After imputation, of the 1 128 635 individuals for whom a mean of the second and third readings was available, 393 924 (34·9%) individuals had hypertension. 153 905 (17·3%) of 888 616 individuals who were not receiving antihypertensive treatment were hypertensive, and 105 456 (46·3%) of the 227 721 individuals receiving treatment did not have controlled blood pressure. Significant differences in adjusted blood pressures and hypertension prevalence were apparent between regions. Adjusted blood pressure was higher in association with antihypertensive medication, diabetes, cerebrovascular disease, smoking, and alcohol consumption. Blood pressure was higher when measured on the right arm than on the left arm, and blood pressure was highest on Saturdays. Interpretation: Inexpensive global screening of blood pressure is achievable using volunteers and convenience sampling. Pending the set-up of systematic surveillance systems worldwide, MMM will be repeated annually to raise awareness of blood pressure. Funding: International Society of Hypertension, Centers for Disease Control and Prevention, Servier Pharmaceutical Co.
- Authors: Beaney, Thomas , Schutte, Aletta , Tomaszewski, Maciej , Ariti, Cono , Burrell, Louise , Castillo, Rafael , Charchar, Fadi , Damasceno, Albertino , Kruger, Ruan , Lackland, Daniel , Nilsson, Peter , Prabhakaran, Dorairaj , Ramirez, Agustin , Schlaich, Markus , Wang, Jiguang , Weber, Michael , Poulter, Neil
- Date: 2018
- Type: Text , Journal article
- Relation: The Lancet Global Health Vol. 6, no. 7 (2018), p. e736-e743
- Full Text:
- Reviewed:
- Description: Background: Increased blood pressure is the biggest contributor to the global burden of disease and mortality. Data suggest that less than half of the population with hypertension is aware of it. May Measurement Month was initiated to raise awareness of the importance of blood pressure and as a pragmatic interim solution to the shortfall in screening programmes. Methods: This cross-sectional survey included volunteer adults (≥18 years) who ideally had not had their blood pressures measured in the past year. Each participant had their blood pressure measured three times and received a a questionnaire about demographic, lifestyle, and environmental factors. The primary objective was to raise awareness of blood pressure, measured by number of countries involved, number of people screened, and number of people who have untreated or inadequately treated hypertension (defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or both, or on the basis of receiving antihypertensive medication). Multiple imputation was used to estimate the mean of the second and third blood pressure readings if these were not recorded. Measures of association were analysed using linear mixed models. Findings: Data were collected from 1 201 570 individuals in 80 countries. After imputation, of the 1 128 635 individuals for whom a mean of the second and third readings was available, 393 924 (34·9%) individuals had hypertension. 153 905 (17·3%) of 888 616 individuals who were not receiving antihypertensive treatment were hypertensive, and 105 456 (46·3%) of the 227 721 individuals receiving treatment did not have controlled blood pressure. Significant differences in adjusted blood pressures and hypertension prevalence were apparent between regions. Adjusted blood pressure was higher in association with antihypertensive medication, diabetes, cerebrovascular disease, smoking, and alcohol consumption. Blood pressure was higher when measured on the right arm than on the left arm, and blood pressure was highest on Saturdays. Interpretation: Inexpensive global screening of blood pressure is achievable using volunteers and convenience sampling. Pending the set-up of systematic surveillance systems worldwide, MMM will be repeated annually to raise awareness of blood pressure. Funding: International Society of Hypertension, Centers for Disease Control and Prevention, Servier Pharmaceutical Co.
A meta-analysis of gene expression signatures of blood pressure and hypertension
- Authors: Charchar, Fadi
- Date: 2015
- Type: Text , Journal article
- Relation: PLoS Genetics Vol. 11, no. 3 (2015), p. 1-29
- Full Text:
- Reviewed:
- Description: Genome-wide association studies (GWAS) have uncovered numerous genetic variants (SNPs) that are associated with blood pressure (BP). Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p<0.05). Among these genes, FOS and PTGS2 have been previously reported to be involved in BP-related processes; the others are novel. The top BP signature genes in aggregate explain 5%–9% of inter-individual variance in BP. Of note, rs3184504 in SH2B3, which was also reported in GWAS to be associated with BP, was found to be a trans regulator of the expression of 6 of the transcripts we found to be associated with BP (FOS, MYADM, PP1R15A, TAGAP, S100A10, and FGBP2). Gene set enrichment analysis suggested that the BP-related global gene expression changes include genes involved in inflammatory response and apoptosis pathways. Our study provides new insights into molecular mechanisms underlying BP regulation, and suggests novel transcriptomic markers for the treatment and prevention of hypertension. **Please note that there are multiple authors for this article therefore only the name of the Federation University Australia affiliate is provided in this record**
- Authors: Charchar, Fadi
- Date: 2015
- Type: Text , Journal article
- Relation: PLoS Genetics Vol. 11, no. 3 (2015), p. 1-29
- Full Text:
- Reviewed:
- Description: Genome-wide association studies (GWAS) have uncovered numerous genetic variants (SNPs) that are associated with blood pressure (BP). Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p<0.05). Among these genes, FOS and PTGS2 have been previously reported to be involved in BP-related processes; the others are novel. The top BP signature genes in aggregate explain 5%–9% of inter-individual variance in BP. Of note, rs3184504 in SH2B3, which was also reported in GWAS to be associated with BP, was found to be a trans regulator of the expression of 6 of the transcripts we found to be associated with BP (FOS, MYADM, PP1R15A, TAGAP, S100A10, and FGBP2). Gene set enrichment analysis suggested that the BP-related global gene expression changes include genes involved in inflammatory response and apoptosis pathways. Our study provides new insights into molecular mechanisms underlying BP regulation, and suggests novel transcriptomic markers for the treatment and prevention of hypertension. **Please note that there are multiple authors for this article therefore only the name of the Federation University Australia affiliate is provided in this record**
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].
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.
The emerging role of non-coding RNA in essential hypertension and blood pressure regulation
- Marques, Francine, Booth, Scott, Charchar, Fadi
- Authors: Marques, Francine , Booth, Scott , Charchar, Fadi
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of Human Hypertension Vol. 29, no. 8 (2015), p. 459-467
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text: false
- Reviewed:
- Description: Unravelling the complete genetic predisposition to high blood pressure (BP) has proven to be challenging. This puzzle and the fact that coding regions of the genome account for less than 2% of the entire human DNA support the hypothesis that genetic mechanism besides coding genes are likely to contribute to BP regulation. Non-coding RNAs (ncRNAs) are emerging as key players of transcription regulation in both health and disease states. They control basic functions in virtually all cell types relevant to the cardiovascular system and, thus, a direct involvement with BP regulation is highly probable. Here, we review the literature about ncRNAs associated with human BP and essential hypertension, highlighting investigations, methodology and difficulties arising in the field. The most investigated ncRNAs so far are microRNAs (miRNAs), small ncRNAs that modulate gene expression by posttranscriptional mechanisms. We discuss studies that have examined miRNAs associated with BP in biological fluids, such as blood and urine, and tissues, such as vascular smooth muscle cells and the kidney. Furthermore, we review the interaction between miRNA binding sites and single nucleotide polymorphisms in genes associated with BP. In conclusion, there is a clear need for more human and functional studies to help elucidate the multifaceted roles of ncRNAs, in particular mid- and long ncRNAs in BP regulation. © 2015 Macmillan Publishers Limited All rights reserved.
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
- 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.
- 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.
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:
- 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
- Reviewed:
- 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.
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