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dc.contributor.authorTanaka, Jun
dc.contributor.authorQiang, Li
dc.contributor.authorBanks, Alexander
dc.contributor.authorWelch, Carrie L.
dc.contributor.authorMatsumoto, Michihiro
dc.contributor.authorKitamura, Tadahiro
dc.contributor.authorIdo-Kitamura, Yukari
dc.contributor.authorDePinho, Ronald A.
dc.contributor.authorAccili, Domenico
dc.date.accessioned2011-11-28T01:39:51Z
dc.date.issued2009
dc.identifier.citationTanaka, Jun, Li Qiang, Alexander S. Banks, Carrie L. Welch, Michihiro Matsumoto, Tadahiro Kitamura, Yukari Ido-Kitamura, Ronald A. DePinho, and Domenico Accili. 2009. Foxo1 Links Hyperglycemia to LDL Oxidation and Endothelial Nitric Oxide Synthase Dysfunction in Vascular Endothelial Cells. Diabetes 58(10): 2344-2354.en_US
dc.identifier.issn0012-1797en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:5352097
dc.description.abstractOBJECTIVE: Atherosclerotic cardiovascular disease is the leading cause of death among people with diabetes. Generation of oxidized LDLs and reduced nitric oxide (NO) availability because of endothelial NO synthase (eNOS) dysfunction are critical events in atherosclerotic plaque formation. Biochemical mechanism leading from hyperglycemia to oxLDL formation and eNOS dysfunction is unknown. RESEARCH DESIGN AND METHODS: We show that glucose, acting through oxidative stress, activates the transcription factor Foxo1 in vascular endothelial cells. RESULTS: Foxo1 promotes inducible NOS (iNOS)-dependent NO-peroxynitrite generation, which leads in turn to LDL oxidation and eNOS dysfunction. We demonstrate that Foxo1 gain-of-function mimics the effects of hyperglycemia on this process, whereas conditional Foxo1 knockout in vascular endothelial cells prevents it. CONCLUSIONS: The findings reveal a hitherto unsuspected role of the endothelial iNOS-NO-peroxynitrite pathway in lipid peroxidation and eNOS dysfunction and suggest that Foxo1 activation in response to hyperglycemia brings about proatherogenic changes in vascular endothelial cell function.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Diabetes Associationen_US
dc.relation.isversionofdoi:10.2337/db09-0167en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2750207/pdf/en_US
dash.licenseLAA
dc.titleFoxo1 Links Hyperglycemia to LDL Oxidation and Endothelial Nitric Oxide Synthase Dysfunction in Vascular Endothelial Cellsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalDiabetesen_US
dash.depositing.authorDePinho, Ronald A.
dc.date.available2011-11-28T01:39:51Z
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dc.identifier.doi10.2337/db09-0167*
dash.contributor.affiliatedBanks, Alexander
dash.contributor.affiliatedDePinho, Ronald A.


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