Severe Acute Respiratory Syndrome Coronavirus 2, COVID-19, and the Renin-Angiotensin System Pressing Needs and Best Research Practices

• Type of Material: Article
• Authors: Matthew A. Sparks, Duke University; Andrew M. South, American Heart Association; Andrew D. Badley, Mayo Clinic; Carissa M. Baker-Smith, Nemours Alfred I duPont Hospital For Children; Daniel Batlle, Northwestern University; Biykem Bozkurt, Baylor College of Medicine; Roberto Cattaneo, Mayo Clinic; Steven D. Crowley, Duke University; Louis J. Dell'Italia, University of Alabama Birmingham; Andria L. Ford, Washington University in St. Louis; Kathy Griendling, Emory University; Susan B. Gurley, American Heart Association; Scott E. Kasner, University of Pennsylvania; Joseph A. Murray, Mayo Clinic; Karl A. Nath, Mayo Clinic; Marc A. Pfeffer, American Heart Association; Janani Rangaswami, American Heart Association; W. Robert Taylor, Emory University; Vesna D. Garovic, Mayo Clinic
• Language: English
• Date: 2020-11-01
• Publisher: LIPPINCOTT WILLIAMS & WILKINS
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020, Wolters Kluwer Health
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15948
• Title of Journal or Parent Work: HYPERTENSION
• Volume: 76
• Issue: 5
• Start Page: 1350
• End Page: 1367
• Grant/Funding Information: ADB- Supported by grants from NIAID (grants AI110173 and AI120698) Amfar (#109593) and Mayo Clinic (HH Shieck Khalifa Bib Zayed Al-Nahyan Named Professorship of Infectious Diseases).; DB- Grants from NIH NIDDK: R01DK104785; MAP- Grants from Novartis; VDG- Grants from NIH: R01-HL136348.; RC- “COVID-19 Virology” by the Mayo COVID-19 Research Taskforce; KKG and WRT- NIH grant P01HL095070; MAS- Grants from Renal Research Institute; SDC- NIH grants DK118019, HL128355; Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Grant BX000893; American Heart Association Grant 18TPA34170047.; AMS- Grants from NIH NHLBI (HL146818, HL148910 and HL148394)
• Keywords: blood pressure; ACE2 EXPRESSION; Cardiovascular System & Cardiology; CONVERTING ENZYME 2; Peripheral Vascular Disease; Life Sciences & Biomedicine; coronavirus; EPITHELIAL-CELLS; SARS CORONAVIRUS; hypertension; AT(2) RECEPTORS; KIDNEY INJURY; FUNCTIONAL RECEPTOR; Science & Technology; II GENERATION; angiotensin II; BLOOD-PRESSURE; CARDIAC DYSFUNCTION; cardiovascular disease

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.