Physiology - Research Publications

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    2020 International Society of Hypertension Global Hypertension Practice Guidelines
    Unger, T ; Borghi, C ; Charchar, F ; Khan, NA ; Poulter, NR ; Prabhakaran, D ; Ramirez, A ; Schlaich, M ; Stergiou, GS ; Tomaszewski, M ; Wainford, RD ; Williams, B ; Schutte, AE (LIPPINCOTT WILLIAMS & WILKINS, 2020-06)
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    Hypertension and renin-angiotensin system blockers are not associated with expression of angiotensin-converting enzyme 2 (ACE2) in the kidney
    Jiang, X ; Eales, JM ; Scannali, D ; Nazgiewicz, A ; Prestes, P ; Maier, M ; Denniff, M ; Xu, X ; Saluja, S ; Cano-Gamez, E ; Wystrychowski, W ; Szulinska, M ; Antczak, A ; Byars, S ; Skrypnik, D ; Glyda, M ; Krol, R ; Zywiec, J ; Zukowska-Szczechowska, E ; Burrell, LM ; Woolf, AS ; Greenstein, A ; Bogdanski, P ; Keavney, B ; Morris, AP ; Heagerty, A ; Williams, B ; Harrap, SB ; Trynka, G ; Samani, NJ ; Guzik, TJ ; Charchar, FJ ; Tomaszewski, M (OXFORD UNIV PRESS, 2020-12-21)
    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 co-expression 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.
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    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, AM ; Adebayo, O ; Abiola, B ; Iwalokun, B ; Tayo, B ; Charchar, F ; Ojo, A ; Cooper, R (JMIR PUBLICATIONS, INC, 2020-01)
    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. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14820.
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    A Guide to the Short, Long and Circular RNAs in Hypertension and Cardiovascular Disease
    Prestes, PR ; Maier, MC ; Woods, BA ; Charchar, FJ (MDPI, 2020-05)
    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.