This Article Full Text Full Text (PDF) All Versions of this Article: 51/3/712    most recent HYPERTENSIONAHA.107.100693v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Der Sarkissian, S. Articles by Raizada, M. K. PubMed PubMed Citation Articles by Der Sarkissian, S. Articles by Raizada, M. K. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Nucleotide Protein UniGene Substance via MeSH Related Collections Gene therapy ACE/Angiotension receptors Physiological and pathological control of gene expression

(Hypertension. 2008;51:712.)
© 2008 American Heart Association, Inc.

Original Articles

Cardiac Overexpression of Angiotensin Converting Enzyme 2 Protects the Heart From Ischemia-Induced Pathophysiology

Shant Der Sarkissian; Justin L. Grobe; Lihui Yuan; Dhruv R. Narielwala; Glenn A. Walter; Michael J. Katovich; Mohan K. Raizada

From the Department of Physiology and Functional Genomics (S.D.S., L.Y., D.R.N., G.A.W., M.K.R.), College of Medicine, and Department of Pharmacodynamics (J.L.G., M.J.K.), College of Pharmacy, University of Florida, Gainesville.

Correspondence to Mohan K. Raizada, Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, FL 32610. E-mail mraizada{at}phys.med.ufl.edu

Angiotensin converting enzyme 2 (ACE2) has been linked to cardiac dysfunction and hypertension-induced cardiac pathophysiology. In this study, we used a gene overexpression approach to investigate the role of ACE2 in cardiac function and remodeling after myocardial infarction. Rats received an intracardiac injection of 4.5x10⁸ lentivirus containing ACE2 cDNA, followed by permanent coronary artery ligation (CAL) of the left anterior descending artery. At 24 hours and 6 weeks after surgery, cardiac functions, viability, and pathophysiology were assessed by MRI) and by histological analysis. At 24 hours post-CAL, left ventricular (LV) anterior wall motion was stunted to the same extent in control CAL and lenti-ACE2–treated CAL rats. However lenti-ACE2–treated CAL rats showed a 60% reduction in delayed contrast-enhanced LV volume after gadodiamide injection, indicating early ischemic protection of myocardium by ACE2. At 6 weeks after CAL, lenti-ACE2 rats demonstrated a complete rescue of cardiac output, a 41% rescue of ejection fraction, a 44% rescue in contractility, a 37% rescue in motion, and a 53% rescue in LV anterior (infracted) wall thinning compared with control CAL rats. No changes were observed in the LV posterior (noninfarcted) wall other than an 81% rescue in motion produced by ACE2 in CAL rats. Finally, infarct size measured by 2,3,5-triphenyl-tetrazolium chloride staining was not significantly different between the ligated groups. These observations demonstrate that cardiac overexpression of ACE2 exerts protective influence on the heart during myocardial infarction by preserving cardiac functions, LV wall motion and contractility, and by attenuating LV wall thinning.

Key Words: ACE2 • heart disease • myocardial infarction • lentiviral vector • gene therapy