Telmisartan mitigates hyperglycemia-induced vascular inflammation by increasing GSK3 beta-Ser(9) phosphorylation in endothelial cells and mouse aortas
DC Field | Value | Language |
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dc.contributor.author | Song, Kee-Ho | - |
dc.contributor.author | Bae, Sun-Ju | - |
dc.contributor.author | Chang, Jiyeon | - |
dc.contributor.author | Park, Jung-Hyun | - |
dc.contributor.author | Jo, Inho | - |
dc.contributor.author | Cho, Kae Won | - |
dc.contributor.author | Cho, Du-Hyong | - |
dc.date.accessioned | 2021-08-11T14:24:24Z | - |
dc.date.available | 2021-08-11T14:24:24Z | - |
dc.date.issued | 2017-09-30 | - |
dc.identifier.issn | 0006-291X | - |
dc.identifier.issn | 1090-2104 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/7200 | - |
dc.description.abstract | Telmisartan, an angiotensin II type 1 receptor blocker (ARB), attenuates hyperglycemia-aggravated vascular inflammation by decreasing IKB kinase beta (IKK beta) expression in endothelial cells. Because glycogen synthase 3 beta (GSK3 beta) is involved in inflammatory process by regulating nuclear factor-KB (NF-kappa B) activity, we investigated whether GSK3 beta mediates telmisartan-ameliorated vascular inflammation in hyperglycemia-treated endothelial cells and high-fat diet (HFD)-fed mice. Telmisartan remarkably induced GSK3 beta-Ser(9) phosphorylation in hyperglycemia-treated endothelial cells that accompanied a decrease in hyperglycemia-induced NF-KB p65-Ser(536) phosphorylation, vascular cell adhesion molecule 1 (VCAM-1) expression, and THP-1 monocyte adhesion. Ectopic expression of GSK3 beta-S9A, a constitutively active mutant of GSK3 beta, significantly restored complete telmisartan-inhibited NF-KB p65-Ser(536) phosphorylation, VCAM-1 expression, and THP-1 monocyte adhesion. In addition, it reversed telmisartan-repressed IKK beta expression. Among the ARB, including losartan and fimasartan, only telmisartan increased GSK3 beta-Ser(9) phosphorylation, and telmisartan-induced GSK3 beta-Ser(9) phosphorylation remained unchanged by pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor gamma (PPAR gamma) antagonist. Finally, in the aortas of HFD-fed mice, telmisartan treatment significantly attenuated HFD-induced upregulation of NF-KB p65-Ser(536) phosphorylation, VCAM-1 expression, and IKK beta expression and downregulation of GSK3 beta-Ser(9) phosphorylation. Taken together, our findings demonstrated that telmisartan ameliorates hyperglycemia-exacerbated vascular inflammation, at least in part, by inducing GSK3 beta-Ser(9) phosphorylation, which consequently inhibits IKK beta expression, NF-KB p65-Ser(536) phosphorylation, and VCAM-1 expression in a PPAR gamma-independent manner. (C) 2017 Elsevier Inc. All rights reserved. | - |
dc.format.extent | 9 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Academic Press | - |
dc.title | Telmisartan mitigates hyperglycemia-induced vascular inflammation by increasing GSK3 beta-Ser(9) phosphorylation in endothelial cells and mouse aortas | - |
dc.type | Article | - |
dc.publisher.location | 미국 | - |
dc.identifier.doi | 10.1016/j.bbrc.2017.07.134 | - |
dc.identifier.scopusid | 2-s2.0-85026350119 | - |
dc.identifier.wosid | 000411169800007 | - |
dc.identifier.bibliographicCitation | Biochemical and Biophysical Research Communications, v.491, no.4, pp 903 - 911 | - |
dc.citation.title | Biochemical and Biophysical Research Communications | - |
dc.citation.volume | 491 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 903 | - |
dc.citation.endPage | 911 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Biophysics | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biophysics | - |
dc.subject.keywordPlus | NF-KAPPA-B | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | DISEASE | - |
dc.subject.keywordPlus | ADHESION | - |
dc.subject.keywordPlus | ATHEROSCLEROSIS | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | SYNTHASE | - |
dc.subject.keywordPlus | TYPE-1 | - |
dc.subject.keywordAuthor | Telmisartan | - |
dc.subject.keywordAuthor | Vascular inflammation | - |
dc.subject.keywordAuthor | Hyperglycemia | - |
dc.subject.keywordAuthor | GSK3 beta | - |
dc.subject.keywordAuthor | VCAM-1 | - |
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