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Protection from angiotensin II‐induced cardiac hypertrophy and fibrosis by systemic lentiviral delivery of ACE2 in rats
Author(s) -
Huentelman Matthew J.,
Grobe Justin L.,
Vazquez Jorge,
Stewart Jillian M.,
Mecca Adam P.,
Katovich Michael J.,
Ferrario Carlos M.,
Raizada Mohan K.
Publication year - 2005
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2005.031096
Subject(s) - angiotensin converting enzyme 2 , angiotensin ii , renin–angiotensin system , cardiac fibrosis , medicine , fibrosis , vasoprotective , myocardial fibrosis , endocrinology , blood pressure , muscle hypertrophy , angiotensin converting enzyme , nitric oxide , disease , covid-19 , infectious disease (medical specialty)
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.