TY  - EJOU
AU  - Eluwole, E. Omotayo Alaba
AU  - Ogunlade, O. Oluwadare
TI  - Targeting ACE2 in the Renin–Angiotensin–Aldosterone System: Post-COVID (Long-Term) Cardiovascular Sequelae
T2  - Journal of Experimental Pharmacology and Toxicology

PY  - 2026
VL  - 4
IS  - 1
SN  - 3091-0595

AB  - 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.
KW  - angiotensin-converting enzyme 2 (ACE2)
KW  - renin–angiotensin–aldosterone system
KW  - angiotensin II
KW  - angiotensin-(1–7)
KW  - cardiovascular disease
KW  - post-COVID-19 complications
DO  - 10.6425/042026jept002