{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:40:09Z","timestamp":1790872809671,"version":"4.1.0"},"reference-count":49,"publisher":"Canadian Science Publishing","issue":"12","license":[{"start":{"date-parts":[[2007,12,1]],"date-time":"2007-12-01T00:00:00Z","timestamp":1196467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:p> Elevation 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<jats:sup>phox<\/jats:sup> 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 p22<jats:sup>phox<\/jats:sup> 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. <\/jats:p>","DOI":"10.1139\/y07-112","type":"journal-article","created":{"date-parts":[[2007,12,7]],"date-time":"2007-12-07T16:17:25Z","timestamp":1197044245000},"page":"1236-1247","source":"Crossref","is-referenced-by-count":72,"title":["Homocysteine stimulates NADPH oxidase-mediated superoxide production leading to endothelial dysfunction in rats"],"prefix":"10.1139","volume":"85","author":[{"given":"Vathsala E.R.","family":"Edirimanne","sequence":"first","affiliation":[{"name":"Department of Animal Science, Department of Physiology, University of Manitoba, Canadian Centre for Agri-Food Research in Medicine, St. Boniface Hospital Research Centre, Winnipeg, MB R2H\u00a02A6, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie W.H.","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Department of Physiology, University of Manitoba, Canadian Centre for Agri-Food Research in Medicine, St. Boniface Hospital Research Centre, Winnipeg, MB R2H\u00a02A6, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaw L.","family":"Siow","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Department of Physiology, University of Manitoba, Canadian Centre for Agri-Food Research in Medicine, St. Boniface Hospital Research Centre, Winnipeg, MB R2H\u00a02A6, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant N.","family":"Pierce","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Department of Physiology, University of Manitoba, Canadian Centre for Agri-Food Research in Medicine, St. Boniface Hospital Research Centre, Winnipeg, MB R2H\u00a02A6, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiu Y.","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Department of Physiology, University of Manitoba, Canadian Centre for Agri-Food Research in Medicine, St. Boniface Hospital Research Centre, Winnipeg, MB R2H\u00a02A6, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karmin","family":"O","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Department of Physiology, University of Manitoba, Canadian Centre for Agri-Food Research in Medicine, St. Boniface Hospital Research Centre, Winnipeg, MB R2H\u00a02A6, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"155","reference":[{"key":"atypb1\/ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2003.11.005"},{"key":"atypb2\/ref2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000108264.67601.2C"},{"key":"atypb3\/ref3","doi-asserted-by":"publisher","DOI":"10.1139\/y05-136"},{"key":"atypb4\/ref4","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1172\/JCI111249","volume":"73","author":"Babior B.M.","year":"1984","journal-title":"J. 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