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Article: Homocysteine stimulates NADPH oxidase-mediated superoxide production leading to endothelial dysfunction in rats

TitleHomocysteine stimulates NADPH oxidase-mediated superoxide production leading to endothelial dysfunction in rats
Authors
Issue Date2007
Citation
Canadian Journal of Physiology and Pharmacology, 2007, v. 85 n. 12, p. 1236-1247 How to Cite?
AbstractElevation of blood homocysteine (Hcy) levels (hyperhomocysteinemia) is a risk factor for cardiovascular disorders. We previously reported that oxidative stress contributed to Hcy-induced inflammatory response in vascular cells. In this study, we investigated whether NADPH oxidase was involved in Hcy-induced superoxide anion accumulation in the aorta, which leads to endothelial dysfunction during hyperhomocysteinemia. Hyperhomocysteinemia was induced in rats fed a high-methionine diet. NADPH oxidase activity and the levels of superoxide and peroxynitrite were markedly increased in aortas isolated from hyperhomocysteinemic rats. Expression of the NADPH oxidase subunit p22 phox increased significantly in these aortas. Administration of an NADPH oxidase inhibitor (apocynin) not only attenuated aortic superoxide and peroxynitrite to control levels but also restored endothelium-dependent relaxation in the aortas of hyperhomocysteinemic rats. Transfection of human endothelial cells or vascular smooth muscle cells with p22phox siRNA to inhibit NADPH oxidase activation effectively abolished Hcy-induced superoxide anion production, thus indicating the direct involvement of NADPH oxidase in elevated superoxide generation in vascular cells. Taken together, these results suggest that Hcy-stimulated superoxide anion production in the vascular wall is mediated through the activation of NADPH oxidase, which leads to endothelial dysfunction during hyperhomocysteinemia. © 2007 NRC Canada.
Persistent Identifierhttp://hdl.handle.net/10722/194403
ISSN
2015 Impact Factor: 1.704
2015 SCImago Journal Rankings: 0.683
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorEdirimanne, VER-
dc.contributor.authorWoo, CWH-
dc.contributor.authorSiow, YL-
dc.contributor.authorPierce, GN-
dc.contributor.authorXie, JY-
dc.contributor.authorKarmin, O-
dc.date.accessioned2014-01-30T03:32:33Z-
dc.date.available2014-01-30T03:32:33Z-
dc.date.issued2007-
dc.identifier.citationCanadian Journal of Physiology and Pharmacology, 2007, v. 85 n. 12, p. 1236-1247-
dc.identifier.issn0008-4212-
dc.identifier.urihttp://hdl.handle.net/10722/194403-
dc.description.abstractElevation of blood homocysteine (Hcy) levels (hyperhomocysteinemia) is a risk factor for cardiovascular disorders. We previously reported that oxidative stress contributed to Hcy-induced inflammatory response in vascular cells. In this study, we investigated whether NADPH oxidase was involved in Hcy-induced superoxide anion accumulation in the aorta, which leads to endothelial dysfunction during hyperhomocysteinemia. Hyperhomocysteinemia was induced in rats fed a high-methionine diet. NADPH oxidase activity and the levels of superoxide and peroxynitrite were markedly increased in aortas isolated from hyperhomocysteinemic rats. Expression of the NADPH oxidase subunit p22 phox increased significantly in these aortas. Administration of an NADPH oxidase inhibitor (apocynin) not only attenuated aortic superoxide and peroxynitrite to control levels but also restored endothelium-dependent relaxation in the aortas of hyperhomocysteinemic rats. Transfection of human endothelial cells or vascular smooth muscle cells with p22phox siRNA to inhibit NADPH oxidase activation effectively abolished Hcy-induced superoxide anion production, thus indicating the direct involvement of NADPH oxidase in elevated superoxide generation in vascular cells. Taken together, these results suggest that Hcy-stimulated superoxide anion production in the vascular wall is mediated through the activation of NADPH oxidase, which leads to endothelial dysfunction during hyperhomocysteinemia. © 2007 NRC Canada.-
dc.languageeng-
dc.relation.ispartofCanadian Journal of Physiology and Pharmacology-
dc.titleHomocysteine stimulates NADPH oxidase-mediated superoxide production leading to endothelial dysfunction in rats-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1139/Y07-112-
dc.identifier.pmid18066125-
dc.identifier.scopuseid_2-s2.0-38949198356-
dc.identifier.volume85-
dc.identifier.issue12-
dc.identifier.spage1236-
dc.identifier.epage1247-
dc.identifier.isiWOS:000252714700004-

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