Protection from angiotensin II-induced cardiac hypertrophy and fibrosis by systemic lentiviral delivery of ACE2 in rats. Exp Physiol 2005 Sep;90(5):783-90
Date
07/29/2005Pubmed ID
16049057DOI
10.1113/expphysiol.2005.031096Scopus ID
2-s2.0-26044453206 (requires institutional sign-in at Scopus site) 219 CitationsAbstract
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 owing 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 200 ng kg-1 min-1 angiotensin II for 4 weeks resulted in an 80 mmHg increase in systolic blood pressure, 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.
Author List
Huentelman MJ, Grobe JL, Vazquez J, Stewart JM, Mecca AP, Katovich MJ, Ferrario CM, Raizada MKAuthor
Justin L. Grobe PhD Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Angiotensin IIAnimals
Animals, Newborn
Blood Pressure
Body Weight
Carboxypeptidases
Cardiomyopathy, Hypertrophic
Endomyocardial Fibrosis
Gene Expression
Genetic Vectors
Heart
Lentivirus
Mice
Myocardium
Organ Size
Peptidyl-Dipeptidase A
Rats
Rats, Sprague-Dawley
Transduction, Genetic
