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Role of the renin–angiotensin–aldosterone and kinin–kallikrein systems in the cardiovascular complications of COVID-19 and long COVID

Cooper, Samantha L.; Boyle, Eleanor; Jefferson, Sophie R.; Heslop, Calum R. A.; Mohan, Pirathini; Mohanraj, Gearry G. J.; Sidow, Hamza A.; Tan, Rory C. P.; Hill, Stephen J.; Woolard, Jeanette

Role of the renin–angiotensin–aldosterone and kinin–kallikrein systems in the cardiovascular complications of COVID-19 and long COVID Thumbnail


Authors

Eleanor Boyle

Sophie R. Jefferson

Calum R. A. Heslop

Pirathini Mohan

Gearry G. J. Mohanraj

Hamza A. Sidow

Rory C. P. Tan

STEPHEN HILL STEVE.HILL@NOTTINGHAM.AC.UK
Professor of Molecular Pharmacology

JEANETTE WOOLARD Jeanette.Woolard@nottingham.ac.uk
Professor of Cardiovascular Physiology and Pharmacology



Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for the COVID-19 pandemic. Patients may present as asymptomatic or demonstrate mild to severe and life-threatening symptoms. Although COVID-19 has a respiratory focus, there are major cardiovascular complications (CVCs) associated with infection. The reported CVCs include myocarditis, heart failure, arrhythmias, thromboembolism and blood pressure abnormalities. These occur, in part, because of dysregulation of the Renin–Angiotensin–Aldosterone System (RAAS) and Kinin–Kallikrein System (KKS). A major route by which SARS-CoV-2 gains cellular entry is via the docking of the viral spike (S) protein to the membrane-bound angiotensin converting enzyme 2 (ACE2). The roles of ACE2 within the cardiovascular and immune systems are vital to ensure homeostasis. The key routes for the development of CVCs and the recently described long COVID have been hypothesised as the direct consequences of the viral S protein/ACE2 axis, downregulation of ACE2 and the resulting damage inflicted by the immune response. Here, we review the impact of COVID-19 on the cardiovascular system, the mechanisms by which dysregulation of the RAAS and KKS can occur following virus infection and the future implications for pharmacological therapies.

Journal Article Type Article
Acceptance Date Jul 29, 2021
Online Publication Date Jul 31, 2021
Publication Date Aug 1, 2021
Deposit Date Aug 6, 2021
Publicly Available Date Aug 6, 2021
Journal International Journal of Molecular Sciences
Print ISSN 1661-6596
Electronic ISSN 1422-0067
Publisher MDPI AG
Peer Reviewed Peer Reviewed
Volume 22
Issue 15
Article Number 8255
DOI https://doi.org/10.3390/ijms22158255
Keywords Inorganic Chemistry; Organic Chemistry; Physical and Theoretical Chemistry; Computer Science Applications; Spectroscopy; Molecular Biology; General Medicine; Catalysis
Public URL https://nottingham-repository.worktribe.com/output/5957194
Publisher URL https://www.mdpi.com/1422-0067/22/15/8255

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