Onset of experimental severe cardiac fibrosis is mediated by overexpression of Angiotensin-converting enzyme 2

Rachel Masson, Stuart A. Nicklin, Margaret Anne Craig, Martin Mcbride, Kirsten Gilday, Paul Gregorevic, James M. Allen, Jeffrey S. Chamberlain, Godfrey Smith, Delyth Graham, Anna F. Dominiczak, Claudio Napoli, Andrew H. Baker

Research output: Contribution to journalArticle

Abstract

Angiotensin-converting enzyme (ACE) 2 is a recently identified homologue of ACE. There is great interest in the therapeutic benefit for ACE2 overexpression in the heart. However, the role of ACE2 in the regulation of cardiac structure and function, as well as maintenance of systemic blood pressure, remains poorly understood. In cell culture, ACE2 overexpression led to markedly increased myocyte volume, assessed in primary rabbit myocytes. To assess ACE2 function in vivo, we used a recombinant adeno-associated virus 6 delivery system to provide 11-week overexpression of ACE2 in the myocardium of stroke-prone spontaneously hypertensive rats. ACE2, as well as the ACE inhibitor enalapril, significantly reduced systolic blood pressure. However, in the heart, ACE2 overexpression resulted in cardiac fibrosis, as assessed by histological analysis with concomitant deficits in ejection fraction and fractional shortening measured by echocardiography. Furthermore, global gene expression profiling demonstrated the activation of profibrotic pathways in the heart mediated by ACE2 gene delivery. This study demonstrates that sustained overexpression of ACE2 in the heart in vivo leads to the onset of severe fibrosis. {Hypertension. 2009;53:694-700.)

Original languageEnglish
Pages (from-to)694-700
Number of pages7
JournalHypertension
Volume53
Issue number4
DOIs
Publication statusPublished - Apr 2009

Keywords

  • Ace2
  • Adeno-associated virus
  • Gene delivery
  • Hypertension
  • Myocardium

ASJC Scopus subject areas

  • Internal Medicine

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    Masson, R., Nicklin, S. A., Craig, M. A., Mcbride, M., Gilday, K., Gregorevic, P., Allen, J. M., Chamberlain, J. S., Smith, G., Graham, D., Dominiczak, A. F., Napoli, C., & Baker, A. H. (2009). Onset of experimental severe cardiac fibrosis is mediated by overexpression of Angiotensin-converting enzyme 2. Hypertension, 53(4), 694-700. https://doi.org/10.1161/HYPERTENSIONAHA.108.122333