ACE-2/Ang (1-7)/Mas axis and the vascular system: vasoprotection to COVID-19-associated vascular disease

Kuriakose, J., Montezano, A. C. and Touyz, R. M. (2021) ACE-2/Ang (1-7)/Mas axis and the vascular system: vasoprotection to COVID-19-associated vascular disease. Clinical Science, 135(2), pp. 387-407. (doi: 10.1042/CS20200480) (PMID:33511992) (PMCID:PMC7846970)

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Abstract

The two axes of the renin–angiotensin system include the classical ACE/Ang II/AT1 axis and the counter-regulatory ACE2/Ang-(1-7)/Mas1 axis. ACE2 is a multifunctional monocarboxypeptidase responsible for generating Ang-(1-7) from Ang II. ACE2 is important in the vascular system where it is found in arterial and venous endothelial cells and arterial smooth muscle cells in many vascular beds. Among the best characterized functions of ACE2 is its role in regulating vascular tone. ACE2 through its effector peptide Ang-(1-7) and receptor Mas1 induces vasodilation and attenuates Ang II-induced vasoconstriction. In endothelial cells activation of the ACE2/Ang-(1-7)/Mas1 axis increases production of the vasodilator’s nitric oxide and prostacyclin’s and in vascular smooth muscle cells it inhibits pro-contractile and pro-inflammatory signaling. Endothelial ACE2 is cleaved by proteases, shed into the circulation and measured as soluble ACE2. Plasma ACE2 activity is increased in cardiovascular disease and may have prognostic significance in disease severity. In addition to its enzymatic function, ACE2 is the receptor for severe acute respiratory syndrome (SARS)-coronavirus (CoV) and SARS-Cov-2, which cause SARS and coronavirus disease-19 (COVID-19) respectively. ACE-2 is thus a double-edged sword: it promotes cardiovascular health while also facilitating the devastations caused by coronaviruses. COVID-19 is associated with cardiovascular disease as a risk factor and as a complication. Mechanisms linking COVID-19 and cardiovascular disease are unclear, but vascular ACE2 may be important. This review focuses on the vascular biology and (patho)physiology of ACE2 in cardiovascular health and disease and briefly discusses the role of vascular ACE2 as a potential mediator of vascular injury in COVID-19.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Montezano, Dr Augusto and Touyz, Professor Rhian and Kuriakose, Jithin
Authors: Kuriakose, J., Montezano, A. C., and Touyz, R. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Clinical Science
Publisher:Portland Press
ISSN:0143-5221
ISSN (Online):1470-8736
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Clinical Science 135(2):387-407
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
305659BHF 4-Year PhD Studentship Award 2018Rhian TouyzBritish Heart Foundation (BHF)FS/18/58/34179CAMS - Cardiovascular Science
303944BHF Centre of ExcellenceRhian TouyzBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science
190615Vascular Noxs as therapeutic targets and biomarkers in hypertensionRhian TouyzBritish Heart Foundation (BHF)CH/12/4/29762Institute of Cardiovascular & Medical Sciences