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Article: Hyperhomocysteinemia Activates Nuclear Factor-κB in Endothelial Cells via Oxidative Stress

TitleHyperhomocysteinemia Activates Nuclear Factor-κB in Endothelial Cells via Oxidative Stress
Authors
Issue Date2004
Citation
Circulation Research, 2004, v. 94 n. 1, p. 28-36 How to Cite?
AbstractHyperhomocysteinemia is an independent risk factor for cardiovascular diseases. Our previous studies demonstrated an important interaction between nuclear factor-κB (NF-κB) activation and homocysteine (Hcy)-induced chemokine expression in vascular smooth muscle cells and macrophages. The objective of the present study was to investigate the in vivo effect of hyperhomocysteinemia on NF-κB activation and the underlying mechanism of Hcy-induced NF-κB activation in endothelial cells. Hyperhomocysteinemia was induced in Sprague-Dawley rats after 4 weeks of a high-methionine diet. The activated form of NF-κB and increased level of superoxide anions were detected in the endothelium of aortas isolated from hyperhomocysteinemic rats. The underlying mechanism of Hcy-induced NF-κB activation was investigated in human umbilical cord vein endothelial cells and in human aortic endothelial cells. Incubation of cells with Hcy (100 μmol/L) activated IκB kinases (IKKα and IKKβ), leading to phosphorylation and subsequent degradation of IκBα. As a consequence, NF-κB nuclear translocation, enhanced NF-κB/DNA binding activity, and increased transcriptional activity occurred. Additional analysis revealed a marked elevation of superoxide anion levels in Hcy-treated cells. Treatment of cells with a superoxide anion scavenger (polyethylene glycol-superoxide dismutase) or IκB kinase inhibitor (prostaglandin A 1) could prevent Hcy-induced activation of IKK kinases and NF-κB in endothelial cells. In conclusion, these results suggest that Hcy-induced superoxide anion production may play a potential role for NF-κB activation in the early stages of atherosclerosis in the vascular wall via activation of IκB kinases.
Persistent Identifierhttp://hdl.handle.net/10722/194401
ISSN
2015 Impact Factor: 11.551
2015 SCImago Journal Rankings: 5.755
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorAu-Yeung, KKW-
dc.contributor.authorWoo, CWH-
dc.contributor.authorSung, FL-
dc.contributor.authorYip, JCW-
dc.contributor.authorSiow, YL-
dc.contributor.authorKarmin, O-
dc.date.accessioned2014-01-30T03:32:32Z-
dc.date.available2014-01-30T03:32:32Z-
dc.date.issued2004-
dc.identifier.citationCirculation Research, 2004, v. 94 n. 1, p. 28-36-
dc.identifier.issn0009-7330-
dc.identifier.urihttp://hdl.handle.net/10722/194401-
dc.description.abstractHyperhomocysteinemia is an independent risk factor for cardiovascular diseases. Our previous studies demonstrated an important interaction between nuclear factor-κB (NF-κB) activation and homocysteine (Hcy)-induced chemokine expression in vascular smooth muscle cells and macrophages. The objective of the present study was to investigate the in vivo effect of hyperhomocysteinemia on NF-κB activation and the underlying mechanism of Hcy-induced NF-κB activation in endothelial cells. Hyperhomocysteinemia was induced in Sprague-Dawley rats after 4 weeks of a high-methionine diet. The activated form of NF-κB and increased level of superoxide anions were detected in the endothelium of aortas isolated from hyperhomocysteinemic rats. The underlying mechanism of Hcy-induced NF-κB activation was investigated in human umbilical cord vein endothelial cells and in human aortic endothelial cells. Incubation of cells with Hcy (100 μmol/L) activated IκB kinases (IKKα and IKKβ), leading to phosphorylation and subsequent degradation of IκBα. As a consequence, NF-κB nuclear translocation, enhanced NF-κB/DNA binding activity, and increased transcriptional activity occurred. Additional analysis revealed a marked elevation of superoxide anion levels in Hcy-treated cells. Treatment of cells with a superoxide anion scavenger (polyethylene glycol-superoxide dismutase) or IκB kinase inhibitor (prostaglandin A 1) could prevent Hcy-induced activation of IKK kinases and NF-κB in endothelial cells. In conclusion, these results suggest that Hcy-induced superoxide anion production may play a potential role for NF-κB activation in the early stages of atherosclerosis in the vascular wall via activation of IκB kinases.-
dc.languageeng-
dc.relation.ispartofCirculation Research-
dc.titleHyperhomocysteinemia Activates Nuclear Factor-κB in Endothelial Cells via Oxidative Stress-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1161/01.RES.0000108264.67601.2C-
dc.identifier.pmid14630727-
dc.identifier.scopuseid_2-s2.0-0347951237-
dc.identifier.volume94-
dc.identifier.issue1-
dc.identifier.spage28-
dc.identifier.epage36-
dc.identifier.isiWOS:000187911700009-

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