Relationship Between ACE2 and Other Components of the Renin-Angiotensin System

Abstract

Purpose of the review: Angiotensin-converting enzyme 2 (ACE2) is a key counter-regulatory component of the renin-angiotensin system. Here, we briefly review the mechanistic and target organ effects related to ACE2 activity, and the importance of ACE2 in SARS-CoV-2 infection.

Recent findings: ACE2 converts angiotensin (Ang) II to Ang-(1-7), which directly opposes the vasoconstrictive, proinflammatory, and prothrombotic effects of Ang II. ACE2 also facilitates SARS-CoV-2 viral entry into host cells. Drugs that interact with the renin-angiotensin system may impact ACE2 expression and COVID-19 pathogenesis; however, the magnitude and direction of these effects are unknown at this time. High quality research is needed to improve our understanding of how agents that act on the renin-angiotensin system impact ACE2 and COVID-19-related disease outcomes.

Keywords: Angiotensin receptor blockers; Angiotensin-converting enzyme; Angiotensin-converting enzyme inhibitors; COVID-19; Cardiovascular disease; Chronic kidney disease; Coronavirus infections; Hypertension; Renin-angiotensin system.

Fig. 1

The counter-regulatory role of ACE2 in the renin-angiotensin system. This figure demonstrates the conversion of angiotensinogen to Ang I by renin, Ang I to Ang II by ACE, and Ang II to Ang-(1–7) by ACE2. Ang II acts on the AT₁R receptor to increase vasoconstriction, fluid and sodium retention by the kidney, and oxidative stress, resulting in increased blood pressure. Ang-(1–7) acts on the Mas receptor resulting in vasodilation, increased fluid and sodium excretion by the kidney, and a reduction in oxidative stress, resulting in reduced blood pressure