Abstract
The coronavirus disease 2019 (COVID-19) pandemic is associated with significant morbidity and mortality throughout the world, predominantly due to lung and cardiovascular injury. The virus responsible for COVID-19 - severe acute respiratory syndrome coronavirus 2 - gains entry into host cells via ACE2 (angiotensin-converting enzyme 2). ACE2 is a primary enzyme within the key counter-regulatory pathway of the renin-angiotensin system (RAS), which acts to oppose the actions of Ang (angiotensin) II by generating Ang-(1-7) to reduce inflammation and fibrosis and mitigate end organ damage. As COVID-19 spans multiple organ systems linked to the cardiovascular system, it is imperative to understand clearly how severe acute respiratory syndrome coronavirus 2 may affect the multifaceted RAS. In addition, recognition of the role of ACE2 and the RAS in COVID-19 has renewed interest in its role in the pathophysiology of cardiovascular disease in general. We provide researchers with a framework of best practices in basic and clinical research to interrogate the RAS using appropriate methodology, especially those who are relatively new to the field. This is crucial, as there are many limitations inherent in investigating the RAS in experimental models and in humans. We discuss sound methodological approaches to quantifying enzyme content and activity (ACE, ACE2), peptides (Ang II, Ang-[1-7]), and receptors (types 1 and 2 Ang II receptors, Mas receptor). Our goal is to ensure appropriate research methodology for investigations of the RAS in patients with severe acute respiratory syndrome coronavirus 2 and COVID-19 to ensure optimal rigor and reproducibility and appropriate interpretation of results from these investigations.
Original language | English (US) |
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Pages (from-to) | 1350-1367 |
Number of pages | 18 |
Journal | Hypertension |
Volume | 76 |
Issue number | 5 |
DOIs | |
State | Published - Nov 1 2020 |
Funding
S.D. Crowley received National Institutes of Health (NIH) grants DK118019, HL128355; Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Grant BX000893; American Heart Association Grant 18TPA34170047. R. Cattaneo is supported by coronavirus disease 2019 (COVID-19) Virology by the Mayo COVID-19 Research Taskforce. A.D. Badley is supported by grants from National Institute of Allergy and Infectious Diseases (grants AI110173 and AI120698) Amfar (No. 109593) and Mayo Clinic (HH Shieck Khalifa Bib Zayed Al-Nahyan Named Professorship of Infectious Diseases). M.A. Pfeffer received grants from Novartis. M.A. Sparks received grants from Renal Research Institute. K. Griendling and W.R. Taylor received NIH grant P01HL095070. A.M. South received grants from NIH National Heart, Lung, and Blood Institute (HL146818, HL148910, and HL148394). V.D. Garovic received grants from NIH: R01-HL136348. D. Batlle received grants from NIH National Institute of Diabetes and Digestive and Kidney Diseases: R01DK104785.
Keywords
- angiotensin II
- blood pressure
- cardiovascular disease
- coronavirus
- hypertension
ASJC Scopus subject areas
- Internal Medicine