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Myocardial infarction increases ACE2 expression in rat and humans.

AIMS: Angiotensin converting enzyme (ACE) 2 catalyses the cleavage of angiotensin (Ang) I to Ang 1-9 and of Ang II to Ang 1-7. ACE2 deficiency impairs cardiac contractility and upregulates hypoxia-induced genes, suggesting a link with myocardial ischaemia. We studied the expression of ACE2 after myocardial infarction (MI) in the rat as well as in human failing hearts. METHODS AND RESULTS: Rats were killed at days 1, 3, and 28 after MI, or treated for 4 weeks with the ACE inhibitor ramipril (1 mg/kg). Cardiac gene and protein expression of ACE and ACE2 were assessed by quantitative real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry/activity assays/in vitro autoradiography, respectively. Both ACE (P = 0.022) and ACE2 (P = 0.015) mRNA increased in the border/infarct area compared with the viable area at day 3 after MI. By day 28, increases in ACE (P = 0.005) and ACE2 (P = 0.006) mRNA were also seen in the viable myocardium of MI rats compared with myocardium of control rats. ACE2 protein localized to macrophages, vascular endothelium, smooth muscle, and myocytes. Ramipril attenuated cardiac hypertrophy and inhibited cardiac ACE. In contrast, ramipril had no effect on cardiac ACE2 mRNA, which remained elevated in all areas of the MI rat heart. Immunoreactivity of both ACE and ACE2 increased in failing human hearts. CONCLUSION: The increase in ACE2 after MI suggests that it plays an important role in the negative modulation of the renin angiotensin system in the generation and degradation of angiotensin peptides after cardiac injury.

Pubmed ID: 15671045


  • Burrell LM
  • Risvanis J
  • Kubota E
  • Dean RG
  • MacDonald PS
  • Lu S
  • Tikellis C
  • Grant SL
  • Lew RA
  • Smith AI
  • Cooper ME
  • Johnston CI


European heart journal

Publication Data

February 8, 2005

Associated Grants


Mesh Terms

  • Aged
  • Angiotensin-Converting Enzyme Inhibitors
  • Animals
  • Carboxypeptidases
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction
  • Myocardium
  • Peptidyl-Dipeptidase A
  • RNA, Messenger
  • Ramipril
  • Rats
  • Rats, Sprague-Dawley
  • Renin-Angiotensin System
  • Reverse Transcriptase Polymerase Chain Reaction