Received May 25, 2005
Revised June 21, 2005
Accepted after revision July 18, 2005
Protection from Angiotensin II-induced Cardiac Hypertrophy and Fibrosis by Systemic Lentiviral Delivery of ACE2
Matthew J Huentelman 1,
Justin L Grobe 1,
Jorge Vazquez 1,
Jillian M Stewart 1,
Adam P Mecca 1,
Michael J Katovich 1,
Carlos M Ferrario 2,
Mohan K Raizada 1*
1 University of Florida
2 Wake Forest University Medical Center
* To whom correspondence should be addressed. E-mail: mraizada{at}phys.med.ufl.edu.
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Abstract |
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Angiotensin converting enzyme 2 (ACE2), a newly discovered member of the renin-angiotensin system (RAS), is a potential therapeutic target for the control of cardiovascular disease due to its key role in the formation of vasoprotective peptides from angiotensin II. The aim of the present study was to evaluate whether overexpression of ACE2 could protect the heart from angiotensin II-induced hypertrophy and fibrosis. Lentiviral vector encoding mouse ACE2 (lenti-mACE2) or GFP was injected intracardially in 5-day-old Sprague-Dawley rats. This resulted in expression of mACE2 in cardiac tissue for the duration of the study. Infusion of 200ng-kg-1 min-1 angiotensin II for four weeks resulted in an 80 mmHg increase in BP, a significant increase in the heart weight to body weight ratio (HW/BW), and marked myocardial fibrosis in control rats. Transduction with lenti-mACE2 resulted in significant attenuation of the increased HW/BW and myocardial fibrosis induced by angiotensin II infusion. These observations demonstrate that ACE2 overexpression results in protective effects on angiotensin II-induced cardiac hypertrophy and fibrosis.
Key Words:
Angiotensin, Cardiovascular, Hypertension
