Glucose increases endothelial-dependent superoxide formation in coronary arteries by NAD(P)H oxidase activation: Attenuation by the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin
Increased vascular superoxide anion (O(2)(-)) formation is essentially involved in the pathophysiology of atherosclerosis. Chronic hyperglycemia induces endothelial dysfunction, probably due to increased formation of reactive oxygen intermediates. However, little is known about the localization, mod...
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Published in | Diabetes (New York, N.Y.) Vol. 51; no. 8; pp. 2648 - 2652 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Alexandria, VA
American Diabetes Association
01.08.2002
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Subjects | |
Online Access | Get full text |
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Summary: | Increased vascular superoxide anion (O(2)(-)) formation is essentially involved in the pathophysiology of atherosclerosis. Chronic hyperglycemia induces endothelial dysfunction, probably due to increased formation of reactive oxygen intermediates. However, little is known about the localization, modulators, and molecular mechanisms of vascular O(2)(-) formation during hyperglycemia. In porcine coronary segments, high glucose significantly increased O(2)(-) formation (1,703.5 +/- 394.9 vs. 834.1 +/- 91.7 units/mg for control, n = 64, P < 0.05; measured by lucigenin-enhanced chemiluminescence). This effect was completely blocked after removal of the endothelium. Coincubation with 10 micromol/l atorvastatin, a lipophilic inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, attenuated basal and glucose-induced O(2)(-) formation (328.1 +/- 46.5 and 332.8 +/- 50.3 units/mg, P < 0.05 vs. without atorvastatin). Incubation with mevalonic acid reversed this effect. High glucose increased mRNA expression of the oxidase subunit p22(phox), which was blocked by 10 micromol/l atorvastatin, whereas expression of gp91(phox) was unchanged. In conclusion, glucose-induced increase of vascular O(2)(-) formation is endothelium dependent and is probably mediated by increased p22(phox) subunit expression. Beneficial effects of statins in diabetic patients may be explained in part by attenuation of vascular O(2)(-) formation independent of lipid lowering. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0012-1797 1939-327X |
DOI: | 10.2337/diabetes.51.8.2648 |