Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 조인호 | * |
dc.contributor.author | 박정현 | * |
dc.date.accessioned | 2017-11-01T05:01:55Z | - |
dc.date.available | 2017-11-01T05:01:55Z | - |
dc.date.issued | 2017 | * |
dc.identifier.issn | 0006-291X | * |
dc.identifier.other | OAK-21137 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/239056 | - |
dc.description.abstract | Telmisartan, an angiotensin II type 1 receptor blocker (ARB), attenuates hyperglycemia-aggravated vascular inflammation by decreasing IκB kinase β (IKKβ) expression in endothelial cells. Because glycogen synthase 3β (GSK3β) is involved in inflammatory process by regulating nuclear factor-κB (NF-κB) activity, we investigated whether GSK3β mediates telmisartan-ameliorated vascular inflammation in hyperglycemia-treated endothelial cells and high-fat diet (HFD)-fed mice. Telmisartan remarkably induced GSK3β-Ser9 phosphorylation in hyperglycemia-treated endothelial cells that accompanied a decrease in hyperglycemia-induced NF-κB p65-Ser536 phosphorylation, vascular cell adhesion molecule-1 (VCAM-1) expression, and THP-1 monocyte adhesion. Ectopic expression of GSK3β-S9A, a constitutively active mutant of GSK3β, significantly restored complete telmisartan-inhibited NF-κB p65-Ser536 phosphorylation, VCAM-1 expression, and THP-1 monocyte adhesion. In addition, it reversed telmisartan-repressed IKKβ expression. Among the ARB, including losartan and fimasartan, only telmisartan increased GSK3β-Ser9 phosphorylation, and telmisartan-induced GSK3β-Ser9 phosphorylation remained unchanged by pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor γ (PPARγ) antagonist. Finally, in the aortas of HFD-fed mice, telmisartan treatment significantly attenuated HFD-induced upregulation of NF-κB p65-Ser536 phosphorylation, VCAM-1 expression, and IKKβ expression and downregulation of GSK3β-Ser9 phosphorylation. Taken together, our findings demonstrated that telmisartan ameliorates hyperglycemia-exacerbated vascular inflammation, at least in part, by inducing GSK3β-Ser9 phosphorylation, which consequently inhibits IKKβ expression, NF-κB p65-Ser536 phosphorylation, and VCAM-1 expression in a PPARγ-independent manner. © 2017 Elsevier Inc. | * |
dc.language | English | * |
dc.publisher | Elsevier B.V. | * |
dc.subject | GSK3β | * |
dc.subject | Hyperglycemia | * |
dc.subject | Telmisartan | * |
dc.subject | Vascular inflammation | * |
dc.subject | VCAM-1 | * |
dc.title | Telmisartan mitigates hyperglycemia-induced vascular inflammation by increasing GSK3β-Ser9 phosphorylation in endothelial cells and mouse aortas | * |
dc.type | Article | * |
dc.relation.issue | 4 | * |
dc.relation.volume | 491 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 903 | * |
dc.relation.lastpage | 911 | * |
dc.relation.journaltitle | Biochemical and Biophysical Research Communications | * |
dc.identifier.doi | 10.1016/j.bbrc.2017.07.134 | * |
dc.identifier.wosid | WOS:000411169800007 | * |
dc.identifier.scopusid | 2-s2.0-85026350119 | * |
dc.author.google | Song K.-H. | * |
dc.author.google | Bae S.-J. | * |
dc.author.google | Chang J. | * |
dc.author.google | Park J.-H. | * |
dc.author.google | Jo I. | * |
dc.author.google | Cho K.W. | * |
dc.author.google | Cho D.-H. | * |
dc.contributor.scopusid | 조인호(26643129000;56663841900) | * |
dc.contributor.scopusid | 박정현(57192816120) | * |
dc.date.modifydate | 20240123112949 | * |