Journal article
Oxidative stress and vascular disease: 2005 Duff lecture
Arteriosclerosis, thrombosis, and vascular biology, Vol.26(4), pp.689-695
04/2006
DOI: 10.1161/01.ATV.0000203525.62147.28
PMID: 16410455
Abstract
There is compelling evidence that oxidative stress plays a key role in the pathophysiology of several major cardiovascular diseases. In atherosclerosis, hypertension, stroke, diabetes, and heart failure, expression of superoxide is increased in blood vessels, and endothelial vasomotor function is impaired, presumably caused in large part by inactivation of nitric oxide by superoxide. Endothelial dysfunction is predictive of cardiovascular risk, and probably plays a key role in the pathophysiology of atherosclerosis and its complications. In preliminary studies in hypercholesterolemic mice and in older humans, we have found high levels of superoxide in the aortic valve, as well as aorta. We speculate that superoxide, in addition to playing a key role in atherogenesis, may play a key role in signaling that leads to calcific aortic valvular stenosis. Antioxidant enzymes, especially the three isoforms of superoxide dismutase (SOD), modulate basal levels of superoxide and protect against vasomotor dysfunction. A common gene variant of extracellular SOD (ecSOD) is associated with increased risk of ischemic heart disease. We have made recombinant adenoviruses to examine cardiovascular effects of ecSOD and its heparin-binding domain. This approach might be used to study the almost 500 other proteins with a heparin-binding domain. Finally, several key unanswered questions in relation to oxidative stress and atherosclerosis are raised, and proposed as fruitful areas of research.
Details
- Title: Subtitle
- Oxidative stress and vascular disease: 2005 Duff lecture
- Creators
- Donald D Heistad - University of Iowa College of Medicine, Iowa City, Iowa 52242-1081, USA
- Resource Type
- Journal article
- Publication Details
- Arteriosclerosis, thrombosis, and vascular biology, Vol.26(4), pp.689-695
- Publisher
- United States
- DOI
- 10.1161/01.ATV.0000203525.62147.28
- PMID
- 16410455
- ISSN
- 1079-5642
- eISSN
- 1524-4636
- Grant note
- DK 54759 / NIDDK NIH HHS DK 52617 / NIDDK NIH HHS NS 24621 / NINDS NIH HHS HL 14388 / NHLBI NIH HHS DK 15843 / NIDDK NIH HHS HL 62984 / NHLBI NIH HHS HL 16066 / NHLBI NIH HHS HL 38901 / NHLBI NIH HHS
- Language
- English
- Date published
- 04/2006
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040557102771
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