%0 Journal Article
%A Eluwole, Omotayo Alaba Eluwole
%A Ogunlade, Oluwadare Ogunlade
%D 2026
%J Journal of Experimental Pharmacology and Toxicology

%@ 3091-0595

%V 4
%N 1
%P 2

%T Targeting ACE2 in the Renin–Angiotensin–Aldosterone System: Post-COVID (Long-Term) Cardiovascular Sequelae
%M doi:10.6425/042026jept002
%U https://j-pharmacol-tox-exp.com/article/4/1/30
%X 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.