The Two Faces of ACE2: The Role of ACE2 Receptor and Its Polymorphisms in Hypertension and COVID-19

Mira Bosso, Thangavel Alphonse Thanaraj, Mohamed Abu-Farha, Muath Alanbaei, Jehad Abubaker, Fahd Al-Mulla, Mira Bosso, Thangavel Alphonse Thanaraj, Mohamed Abu-Farha, Muath Alanbaei, Jehad Abubaker, Fahd Al-Mulla

Abstract

The mechanism for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires the binding of the virus to the angiotensin-converting enzyme 2 (ACE2) receptor, well-known for its role in counteracting ACE. ACE2 is involved in modulating blood pressure and establishing blood pressure homeostasis. Recently, a critical debatable question has arisen whether using antihypertensive medications will have a favorable impact on people infected with SARS-CoV-2 or a deleterious one, mainly because angiotensin-converting enzyme inhibitor (ACEI) and angiotensin-receptor blocker (ARB) therapy can modulate the expression of ACE2 protein. The concern is that the use of ACEIs and ARBs will increase the expression of ACE2 and increase patient susceptibility to viral host cell entry and propagation. On the other hand, several genetic association studies have examined the relationship between ACE2 genetic variants and the risk of developing hypertension in different ethnic populations. In this review, we discuss the ongoing arguments in the literature about ACE2's role in mortality rate among coronavirus disease 2019 (COVID-19) patients comorbid with hypertension and critically evaluate the current debate about the usage or discontinuation of ACEI/ARB antihypertensive drugs. Moreover, we explore the two opposing roles that ACE2 genetic variants might be playing in COVID-19 by reducing ACE2 receptor effectiveness and mitigating SARS-CoV-2 infectivity.

Keywords: ACE2; ACEI; ARBs; SARS-CoV-2; angiotensin-renin system; genetic variants; hypertension.

© 2020 Dasman Diabetes Institute.

Figures

Graphical abstract
Graphical abstract
Figure 1
Figure 1
ACE2 in the Entry of SARS-CoV-2 into the Host Cell Illustration of the two key arms in the renin-angiotensin system.

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