Faculty Collaboration Database

Cardiac overexpression of angiotensin converting enzyme 2 protects the heart from ischemia-induced pathophysiology. Hypertension 2008 Mar;51(3):712-8

Date

02/06/2008

Pubmed ID

18250366

DOI

10.1161/HYPERTENSIONAHA.107.100693

Scopus ID

2-s2.0-39749202869 (requires institutional sign-in at Scopus site)   129 Citations

Abstract

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 4.5x10(8) 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.

Author List

Der Sarkissian S, Grobe JL, Yuan L, Narielwala DR, Walter GA, Katovich MJ, Raizada MK

Author

Justin L. Grobe PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
DNA, Complementary
Disease Models, Animal
Gene Expression Regulation, Enzymologic
Genetic Therapy
Heart
Lentivirus
Magnetic Resonance Imaging
Male
Myocardial Contraction
Myocardial Infarction
Myocardial Ischemia
Myocardium
Peptidyl-Dipeptidase A
RNA, Messenger
Rats
Rats, Sprague-Dawley
Stroke Volume
Transduction, Genetic
Ventricular Function, Left