Gene transfer of extracellular superoxide dismutase improves endothelial function in rats with heart failure

Shinichiro Iida; Yi Chu; Joseph Francis; Robert M Weiss; Carol A Gunnett; Frank M Faraci; Donald D Heistad

doi:10.1152/ajpheart.00108.2005

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Gene transfer of extracellular superoxide dismutase improves endothelial function in rats with heart failure

Journal article

Peer reviewed

Gene transfer of extracellular superoxide dismutase improves endothelial function in rats with heart failure

Shinichiro Iida, Yi Chu, Joseph Francis, Robert M Weiss, Carol A Gunnett, Frank M Faraci and Donald D Heistad

American journal of physiology. Heart and circulatory physiology, Vol.289(2), pp.H525-532

08/2005

DOI: 10.1152/ajpheart.00108.2005

PMID: 16014615

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Abstract

Oxidative stress is associated with endothelial dysfunction in heart failure. The goals of this study were to determine whether 1) gene transfer of extracellular superoxide dismutase (ecSOD) reduces levels of superoxide and improves endothelial function in the aorta and mesenteric artery in rats with heart failure, and 2) the heparin-binding domain (HBD) of ecSOD, by which ecSOD binds to cells, is required for protective effects of ecSOD. Seven weeks after coronary ligation, in rats with heart failure and sham-operated rats, we injected adenoviral vectors intravenously that express ecSOD, ecSOD with deletion of the HBD (ecSODDeltaHBD), or a control vector. Four days after injection of viruses, responses to acetylcholine, ADP, and sodium nitroprusside were examined in rings of the aorta and mesenteric artery. ecSOD bound to endothelium and increased SOD activity in the aorta after gene transfer of ecSOD, not ecSODDeltaHBD. Gene transfer of ecSOD, but not ecSODDeltaHBD, reduced levels of superoxide and improved relaxation to acetylcholine and ADP in the aorta and mesenteric artery from rats with heart failure. Improvement of relaxation to acetylcholine in the mesenteric artery from rats with heart failure after gene transfer of ecSOD was mediated in part by hydrogen peroxide. The major finding of this study is that the HBD of ecSOD is necessary for protection against endothelial dysfunction in rats with heart failure. We speculate that a common gene variant in the HBD of ecSOD, which is a risk factor for ischemic heart disease, may be a risk factor for vascular maladaptation and endothelial dysfunction in heart failure.

Protein Structure, Tertiary

Gene Transfer Techniques

Heparin - metabolism

Superoxide Dismutase - genetics

Mesenteric Arteries - physiopathology

Humans

Endothelium, Vascular - physiopathology

Rats

Male

Cardiac Output, Low - metabolism

Aorta - metabolism

Cardiac Output, Low - physiopathology

Mesenteric Arteries - metabolism

Rats, Sprague-Dawley

Vasodilation

Hydrogen Peroxide - metabolism

Tissue Distribution

Animals

Endothelium, Vascular - metabolism

Vasomotor System - physiopathology

Superoxides - metabolism

Cardiac Output, Low - therapy

Aorta - physiopathology

Superoxide Dismutase - metabolism

Details

Title: Subtitle: Gene transfer of extracellular superoxide dismutase improves endothelial function in rats with heart failure
Creators: Shinichiro Iida - Cardiovascular Center and Dept. of Internal Medicine, Univ. of Iowa Roy J. and Lucille A Carver, College of Medicine, Iowa City, IA 52242, USA
Yi Chu
Joseph Francis
Robert M Weiss
Carol A Gunnett
Frank M Faraci
Donald D Heistad
Resource Type: Journal article
Publication Details: American journal of physiology. Heart and circulatory physiology, Vol.289(2), pp.H525-532
Publisher: United States
DOI: 10.1152/ajpheart.00108.2005
PMID: 16014615
ISSN: 0363-6135
eISSN: 1522-1539
Grant note: DK-54759 / NIDDK NIH HHS HL-16066 / NHLBI NIH HHS NS-24621 / NINDS NIH HHS DK-15843 / NIDDK NIH HHS HL-62984 / NHLBI NIH HHS DK-52617 / NIDDK NIH HHS HL-55006 / NHLBI NIH HHS
Language: English
Date published: 08/2005
Academic Unit: Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040448202771

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