Angiotensin-Converting Enzyme 2 as a Therapeutic Target for Heart Failure

Abstract

The renin-angiotensin system (RAS) plays a major role in the pathophysiology of cardiovascular disorders. Angiotensin II (Ang-II), the final product of this pathway, is known for its vasoconstrictive and proliferative effects. Angiotensin-converting enzyme 2 (ACE2), a newly discovered homolog of ACE, plays a key role as the central negative regulator of the RAS. It diverts the generation of vasoactive Ang-II into the vasodilatory and growth inhibiting peptide angiotensin(1-7) [Ang(1-7)], thereby providing counter-regulatory responses to neurohormonal activation. There is substantial experimental evidence evaluating the role of ACE2/Ang(1-7) in hypertension, heart failure, and atherosclerosis. In this review, we aim to focus on the conceptual facts of the ACE2-Ang(1-7) axis with regards to clinical implications and therapeutic targets in cardiovascular disorders, with emphasis on the potential therapeutic role in cardiovascular diseases.

Angiotensin-converting enzyme 2 inhibits high-mobility group box 1 and attenuates cardiac dysfunction post-myocardial ischemia

“…This reversal appears to be a combination effect of an upregulation of Ang-(1–7) and AT2R and a downregulation of AngII and ACE. It is well recognized that the AngII/AT1R axis induces maladaptive remodeling in the heart after injury, while the vasoprotective axis, ACE2/Ang-(1–7)/AT2R/Mas R, reverses/prevents this adverse cardiac remodeling [45]. Furthermore, we demonstrated that these ACE2 mediated cardioprotective effects in the ischemic heart are tightly associated with reduction in HMGB1 levels after MI.…”

Plasma and tissue angiotensin‐converting enzyme 2 activity and plasma equilibrium concentrations of angiotensin peptides in dogs with heart disease

“…The counter regulatory role of ACE2 on the maladaptive effects of ACE and AT2(1-8) make ACE2 and its related APs attractive targets for pharmacotherapy. 23,[25][26][27]45,[59][60][61] Treatment with exogenous ACE2 is particularly interesting in light of the fact that the affinity of ACE2 to cleave AT2…”

Lipid-lowering therapy and renin-angiotensin-aldosterone system inhibitors in the era of the COVID-19 pandemic

“…ACE2 gene expression is affected by several factors, including gender (ACE2 gene is X-linked), ACE2 gene polymorphisms, comorbidities (increased in the presence of CVD, hypertension, diabetes), and drug therapy [6]. With regard to drugs, angiotensin II receptor blockers (ARBs) and mineralocorticoid receptor antagonists (MRA) have been reported to raise ACE2 activity in human and animal studies [7]. There are only a few animal studies available showing that statins may also increase ACE2 activity [8,9].…”