title: Angiotensin-converting enzyme 2 is a key modulator of the renin-angiotensin system in cardiovascular and renal disease.
abstract: OBJECTIVE
  Angiotensin-converting enzyme 2 (ACE2) has recently emerged as a key regulator of the renin-angiotensin system in both health and disease.
  
  
  RESULTS
  ACE2 deficiency is associated with elevated tissue and circulating levels of angiotensin II and reduced levels of angiotensin 1-7. Phenotypically, this results in a modest elevation in systolic blood pressure and left ventricular hypertrophy. In atherosclerosis-prone apolipoprotein E knockout mice, ACE2 deficiency results in augmented vascular inflammation and an inflammatory response that contributes to increased atherosclerotic plaque formation. In the kidney, ACE2 deficiency is associated with progressive glomerulosclerosis. Interventions such as ACE2 replenishment or augmentation of its actions have proven successful in reducing hypertension, plaque accumulation, and renal and cardiac damage in a range of different models. Although promising, the balance of the renin-angiotensin system remains complicated, with some evidence that overexpression of ACE2 may have adverse cardiac effects, and ACE2 and its metabolic products may promote epithelial-to-mesenchymal transition.
  
  
  CONCLUSIONS
  Repletion of ACE2's activities offers a new strategy to complement current clinical interventions in treating hypertension, renal and cardiovascular disease. In particular conditions where ACE inhibition and angiotensin receptor blockade are partially effective, the adjunctive actions of ACE2 may not only reduce clinical escape but also augment the efficacy of interventions.
authors.affiliation: Division of Diabetic Complications, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia. chris.tikellis@bakeridi.edu.au
authors.forename: Chris
authors.initials: C
authors.lastname: Tikellis
authors.forename: Stella
authors.initials: S
authors.lastname: Bernardi
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Burns
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D050197:Atherosclerosis / Q000209:etiology; D002318:Cardiovascular Diseases / Q000209:etiology*; D002908:Chronic Disease; D006801:Humans; D006973:Hypertension / Q000209:etiology; D007674:Kidney Diseases / Q000209:etiology*; D009206:Myocardium / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000172:deficiency / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2