Targeting ACE2 in the Renin–Angiotensin–Aldosterone System: Post-COVID (Long-Term) Cardiovascular Sequelae
1 Department of Medical Therapeutics and Pharmacology, Faculty of Basic Clinical Sciences, Obafemi Awolowo University, PMB 220005, Nigeria
2 Department of Physiological Sciences, Faculty of Basic Medical Sciences, Obafemi Awolowo University, PMB 220005, Nigeria
* Author to whom correspondence should be addressed.
Received: 15 Jan 2026 / Accepted: 13 May 2026 / Published: 15 Jun 2026
Abstract
Cardiovascular diseases (CVDs) and the coronavirus disease 2019 (COVID-19) pandemic represent major, interrelated global health challenges, largely mediated by dysregulation of the renin–angiotensin–aldosterone system (RAAS). Traditionally, therapeutic strategies have focused on inhibiting the classical ACE/angiotensin II (Ang II)/AT1 receptor axis, which drives vasoconstriction, inflammation, fibrosis, and cardiovascular remodeling. However, the discovery of angiotensin-converting enzyme 2 (ACE2) has revealed an alternative, counter-regulatory RAAS pathway with significant physiological and therapeutic relevance, particularly in the context of COVID-19. ACE2 catalyzes the conversion of Ang II to angiotensin-(1–7), thereby activating the Mas receptor axis, which exerts vasodilatory, anti-inflammatory, antifibrotic, and antioxidative effects. SARS-CoV-2-induced downregulation of ACE2 disrupts this protective pathway, contributing to cardiovascular injury and post-COVID-19 complications. This review examines classical and alternative RAAS signaling, elucidates the molecular basis of ACE2-mediated cardioprotection, and critically evaluates emerging therapeutic strategies, including natural products targeting the ACE2/angiotensin-(1–7)/Mas receptor axis in cardiovascular disease and post-COVID-19 complications.
Keywords: angiotensin-converting enzyme 2 (ACE2); renin–angiotensin–aldosterone system; angiotensin II; angiotensin-(1–7); cardiovascular disease; post-COVID-19 complications
OPEN ACCESS
This is an open access article distributed under the Creative Commons Attribution
License which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited. (CC BY 4.0).
CITE
Eluwole, O.A.; Ogunlade, O. Targeting ACE2 in the Renin–Angiotensin–Aldosterone System: Post-COVID (Long-Term) Cardiovascular Sequelae. JEPT 2026, 4, 2.
Eluwole OA, Ogunlade O. Targeting ACE2 in the Renin–Angiotensin–Aldosterone System: Post-COVID (Long-Term) Cardiovascular Sequelae. JEPT. 2026; 4(1):2.
Eluwole, Omotayo Alaba; Ogunlade, Oluwadare. 2026. "Targeting ACE2 in the Renin–Angiotensin–Aldosterone System: Post-COVID (Long-Term) Cardiovascular Sequelae." JEPT 4, no. 1: 2.
Not implemented
SHARE
