A story of two ACEs

J Mol Med (Berl). 2003 Apr;81(4):227-34. doi: 10.1007/s00109-003-0419-x. Epub 2003 Mar 28.


According to the World Health Organization predictions cardiovascular diseases will be the leading cause of death by the year 2020. High blood pressure is a major risk factor for myocardial infarction, cerebrovascular disease, and stroke. Modulation of the renin-angiotensin system, particularly inhibition of the angiotensin-converting enzyme (ACE), has become a prime strategy in the treatment of hypertension and heart failure. Recently the gene of a new ACE, termed ACE2, has been characterized. The ACE2 gene maps to defined quantitative trait loci on the X chromosome in three different rat models of hypertension, suggesting ACE2 as a candidate gene for hypertension. In mice the targeted disruption of ACE2 resulted in increased systemic angiotensin II levels, impaired cardiac contractility, and upregulation of hypoxia-induced genes in the heart. Since mice deficient in both ACE2 and ACE show completely normal heart function, it appears that ACE and ACE2 negatively regulate each other. The mechanisms and physiological significance of the interplay between ACE and ACE2 are not yet elucidated, but it may involve several new peptides and peptide systems. In view of drug development the increasing complexity of the renin-angiotensin system offers both challenge and opportunity to develop new and refined treatment strategies against cardiovascular diseases.

Publication types

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

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Blood Pressure
  • Carboxypeptidases / genetics*
  • Carboxypeptidases / physiology
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / therapy
  • DNA, Complementary / metabolism
  • Disease Models, Animal
  • Humans
  • Hypertension / genetics
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Myocardial Contraction
  • Peptidyl-Dipeptidase A / genetics*
  • Peptidyl-Dipeptidase A / physiology*
  • Protein Structure, Tertiary
  • Rats
  • Renin-Angiotensin System
  • Substrate Specificity
  • Up-Regulation


  • DNA, Complementary
  • Carboxypeptidases
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Ace2 protein, rat
  • Angiotensin-Converting Enzyme 2