European Heart Journal Advance Access originally published online on January 25, 2005
European Heart Journal 2005 26(4):369-375; doi:10.1093/eurheartj/ehi114
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Myocardial infarction increases ACE2 expression in rat and humans
1Department of Medicine, University of Melbourne, Austin Health, Repatriation Heidelberg Hospital, Heidelberg 3081, Victoria, Australia
2Vascular Division, Wynn Domain, Baker Heart Research Institute, Melbourne, Australia
3Heart Failure and Transplant Unit, St Vincent's Hospital, Darlinghurst, Sydney, New South Wales, Australia
Received 7 April 2004; revised 30 November 2004; accepted 2 December 2004; online publish-ahead-of-print 24 January 2005.
* Corresponding author. Tel: +61 3 9496 2159; fax: +61 3 9497 4554. E-mail address: l.burrell{at}unimelb.edu.au
See page 322 for the editorial comment on this article (doi:10.1093/eurheartj/ehi043)
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.
Key Words: Myocardium • Infarction • Injury • Heart failure
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