Journal article
Vascular effects of a common gene variant of extracellular superoxide dismutase in heart failure
American journal of physiology. Heart and circulatory physiology, Vol.291(2), pp.H914-920
08/2006
DOI: 10.1152/ajpheart.00080.2006
PMID: 16840738
Abstract
A common gene variant of human extracellular superoxide dismutase (ecSOD), in approximately 5% of humans, is associated with increased risk of ischemic heart disease. The purpose of this study was to examine vascular effects of ecSOD with effects of the ecSOD variant (ecSOD(R213G)) in rats with heart failure. Seven weeks after coronary artery ligation, we studied rats with heart failure and sham-operated rats. Adenoviral vectors expressing human ecSOD, ecSOD(R213G), or a control virus were injected intravenously. In the aorta from rats with heart failure, responses to acetylcholine (69 +/- 4% relaxation, means +/- SE) and basal levels of nitric oxide (NO) (vasoconstrictor responses to a NO synthase inhibitor) were greatly impaired, and levels of superoxide and peroxynitrite were increased. Gene transfer of ecSOD restored responses to acetylcholine (92 +/- 2% relaxation) and basal levels of NO to normal and reduced levels of superoxide [from 2.3 +/- 0.2 to 0.9 +/- 0.2 relative light units per second per millimeter squared (RLU x s(-1) x mm(-2))] and peroxynitrite (from 2.4 +/- 0.2 to 0.9 +/- 0.1 RLU x s(-1) x mm(-2)) in the aorta from rats with heart failure. Gene transfer of ecSOD(R213G) produced little or no improvement. Responses to nitroprusside were not different among the groups. Expression of endogenous mRNA for SODs (CuZnSOD, MnSOD, and ecSOD) and endothelial NOS in the aorta was not different among the groups. In contrast to ecSOD, gene transfer of ecSOD(R213G) in rats with heart failure has minimal beneficial effect on oxidative stress, endothelial function, or basal bioavailability of NO. We speculate that greatly diminished efficacy of ecSOD(R213G) in protection against oxidative stress and endothelial dysfunction may contribute to increased risk of cardiovascular disease in humans with ecSOD(R213G).
Details
- Title: Subtitle
- Vascular effects of a common gene variant of extracellular superoxide dismutase in heart failure
- Creators
- Shinichiro Iida - Department of Internal Medicine, Cardiovascular Center, Univ. of Iowa Roy J. and Lucille A. Carver, College of Medicine Iowa City, IA 52242, USAYi ChuRobert M WeissYu Ming KangFrank M FaraciDonald D Heistad
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.291(2), pp.H914-920
- Publisher
- United States
- DOI
- 10.1152/ajpheart.00080.2006
- PMID
- 16840738
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Grant note
- DK-54759 / NIDDK NIH HHS HL-16066 / NHLBI NIH HHS HL-38901 / NHLBI NIH HHS NS-24621 / NINDS NIH HHS DK-15843 / NIDDK NIH HHS HL-62984 / NHLBI NIH HHS HL-14388 / NHLBI NIH HHS DK-52617 / NIDDK NIH HHS HL-55006 / NHLBI NIH HHS
- Language
- English
- Date published
- 08/2006
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040488202771
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