Telmisartan mitigates hyperglycemia-induced vascular inflammation by increasing GSK3 beta-Ser(9) phosphorylation in endothelial cells and mouse aortas
- Authors
- Song, Kee-Ho; Bae, Sun-Ju; Chang, Jiyeon; Park, Jung-Hyun; Jo, Inho; Cho, Kae Won; Cho, Du-Hyong
- Issue Date
- 30-Sep-2017
- Publisher
- Academic Press
- Keywords
- Telmisartan; Vascular inflammation; Hyperglycemia; GSK3 beta; VCAM-1
- Citation
- Biochemical and Biophysical Research Communications, v.491, no.4, pp 903 - 911
- Pages
- 9
- Journal Title
- Biochemical and Biophysical Research Communications
- Volume
- 491
- Number
- 4
- Start Page
- 903
- End Page
- 911
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/7200
- DOI
- 10.1016/j.bbrc.2017.07.134
- ISSN
- 0006-291X
1090-2104
- 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.
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