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

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.

Citation

Cooper, S. L., Boyle, E., Jefferson, S. R., Heslop, C. R. A., Mohan, P., Mohanraj, G. G. J., Sidow, H. A., Tan, R. C. P., Hill, S. J., & Woolard, J. (2021). Role of the renin–angiotensin–aldosterone and kinin–kallikrein systems in the cardiovascular complications of COVID-19 and long COVID. International Journal of Molecular Sciences, 22(15), Article 8255. https://doi.org/10.3390/ijms22158255

• 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
• 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