Telmisartan attenuates hyperglycemia-exacerbated VCAM-1 expression and monocytes adhesion in TNFα-stimulated endothelial cells by inhibiting IKKβ expression

Kee Ho Song, Jung Hyun Park, Inho Jo, Joong Yeol Park, Jungwon Seo, Soon Ae Kim, Du Hyong Cho

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Uncontrolled hyperglycemia accelerates endothelial damage and vascular inflammation caused by proinflammatory cytokines including tumor necrosis factor α (TNFα), which leads to arteriosclerotic cardiovascular diseases such as myocardial infarction. Telmisartan, an angiotensin II type 1 receptor blocker (ARB), is prescribed for treatment of hypertensive patients with concurrent diabetes mellitus (DM). Although a few clinical trials have suggested that telmisartan decreases cardiovascular complications in diabetic patients, the molecular mechanism for the beneficial effects remains elusive. Here, we investigated a molecular mechanism and effects of telmisartan on the expression of vascular cell adhesion molecule-1 (VCAM-1) and attachment of monocytes onto endothelial cells induced by TNFα in hyperglycemia-treated bovine aortic endothelial cells (BAEC). Telmisartan dose-dependently decreased hyperglycemia-aggravated IκB kinase β (IKKβ) expression and nuclear factor-κB (NF-κB) p65-Ser536 phosphorylation, which accompanied a decrease in VCAM-1 expression and THP-1 monocytes adhesion. Among ARBs, including losartan and fimasartan, only telmisartan showed the inhibitory effects on expression of VCAM-1 and IKKβ, and phosphorylation of NF-κB p65-Ser536. The telmisartan's beneficial effects were not changed by pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor γ (PPARγ) antagonist, although GW9662 clearly inhibited rosiglitazone-induced CD36 expression. Finally, ectopic expression of wild type (WT)-IKKβ significantly restored telmisartan-attenuated VCAM-1 expression, NF-κB p65-Ser536 phosphorylation, and THP-1 monocytes adhesion. Taken together, our findings demonstrate that telmisartan ameliorates hyperglycemia-exacerbated vascular inflammation, at least in part, by decreasing expression of IKKβ and VCAM-1 independently of PPARγ. Telmisartan may be useful for the treatment of DM-associated vascular inflammation and cardiovascular diseases.

Original languageEnglish
Pages (from-to)43-52
Number of pages10
JournalVascular Pharmacology
Volume78
DOIs
StatePublished - 1 Mar 2016

Bibliographical note

Funding Information:
This paper was written as part of Konkuk University's research support program for its faculty on sabbatical leave in 2009 and this work was also supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2008-0062484).

Publisher Copyright:
© 2015 Elsevier Inc.

Keywords

  • Fimasartan (PubChem CID: 9,870,652)
  • Hyperglycemia
  • IKKβ
  • Losartan (PubChem CID: 3961)
  • Telmisartan
  • Telmisartan (PubChem CID: 65,999)
  • VCAM-1
  • Vascular inflammation

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