Targeting angiotensin-converting enzyme 2 as a new therapeutic target for cardiovascular diseases

Can J Physiol Pharmacol. 2014 Jul;92(7):558-65. doi: 10.1139/cjpp-2013-0488. Epub 2014 Apr 8.

Abstract

Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that metabolizes several vasoactive peptides, including angiotensin II (Ang-II; a vasoconstrictive/proliferative peptide), which it converts to Ang-(1-7). Ang-(1-7) acts through the Mas receptor to mediate vasodilatory/antiproliferative actions. The renin-angiotensin system involving the ACE-Ang-II-Ang-II type-1 receptor (AT1R) axis is antagonized by the ACE2-Ang-(1-7)-Mas receptor axis. Loss of ACE2 enhances adverse remodeling and susceptibility to pressure and volume overload. Human recombinant ACE2 may act to suppress myocardial hypertrophy, fibrosis, inflammation, and diastolic dysfunction in heart failure patients. The ACE2-Ang-(1-7)-Mas axis may present a new therapeutic target for the treatment of heart failure patients. This review is mainly focused on the analysis of ACE2, including its influence and potentially positive effects, as well as the potential use of human recombinant ACE2 as a novel therapy for the treatment cardiovascular diseases, such as hypertension and heart failure.

Keywords: ACE2; ECA2; heart failure; insuffisance cardiaque; renin–angiotensin system; système rénine–angiotensine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Heart Failure / drug therapy*
  • Heart Failure / pathology
  • Heart Failure / physiopathology
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / metabolism
  • Hypertension / pathology
  • Hypertension / physiopathology
  • Peptidyl-Dipeptidase A / metabolism*
  • Peptidyl-Dipeptidase A / therapeutic use
  • Reactive Oxygen Species / metabolism
  • Recombinant Proteins / therapeutic use
  • Renin-Angiotensin System
  • Signal Transduction

Substances

  • Reactive Oxygen Species
  • Recombinant Proteins
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2