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Telmisartan mitigates hyperglycemia-induced vascular inflammation by increasing GSK3β-Ser9 phosphorylation in endothelial cells and mouse aortas
- Telmisartan mitigates hyperglycemia-induced vascular inflammation by increasing GSK3β-Ser9 phosphorylation in endothelial cells and mouse aortas
- Song K.-H.; Bae S.-J.; Chang J.; Park J.-H.; Jo I.; Cho K.W.; Cho D.-H.
- Ewha Authors
- 조인호; 박정현
- SCOPUS Author ID
- 조인호; 박정현
- Issue Date
- Journal Title
- Biochemical and Biophysical Research Communications
- vol. 491, no. 4, pp. 903 - 911
- GSK3β; Hyperglycemia; Telmisartan; Vascular inflammation; VCAM-1
- Elsevier B.V.
- SCI; SCIE; SCOPUS
- 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.
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