Protection from angiotensin II-induced cardiac hypertrophy and fibrosis by systemic lentiviral delivery of ACE2 in rats.
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.
Huentelman
Matthew J
MJ
Department of Physiology and Functional Genomics, University of Florida, College of Medicine, PO Box 100274, Gainesville, FL 32610, USA.
Grobe
Justin L
JL
Vazquez
Jorge
J
Stewart
Jillian M
JM
Mecca
Adam P
AP
Katovich
Michael J
MJ
Ferrario
Carlos M
CM
Raizada
Mohan K
MK
D000804:Angiotensin II / Q000494:pharmacology*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D002268:Carboxypeptidases / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D002312:Cardiomyopathy, Hypertrophic / Q000517:prevention & control*; D004719:Endomyocardial Fibrosis / Q000517:prevention & control*; D015870:Gene Expression; D005822:Genetic Vectors; D006321:Heart / Q000187:drug effects; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A; D051381:Rats; D017207:Rats, Sprague-Dawley; D014161:Transduction, Genetic
D000804:Angiotensin II; D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2