Telmisartan inhibits the proinflammatory effects of homocysteine on human endothelial cells through activation of the peroxisome proliferator-activated receptor-δ pathway

Xu,Shanghua; Song,Huanhuan; Huang,Maozhi; Wang,Kefeng; Xu,Changsheng; Xie,Liangdi

doi:10.3892/ijmm.2014.1834

Telmisartan inhibits the proinflammatory effects of homocysteine on human endothelial cells through activation of the peroxisome proliferator-activated receptor-δ pathway

Authors:
- Shanghua Xu
- Huanhuan Song
- Maozhi Huang
- Kefeng Wang
- Changsheng Xu
- Liangdi Xie
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Affiliations: Department of Cardiology, Nanping First Hospital Affiliated to Fujian Medical University, Nanping, Fujian 353000, P.R. China, People's Hospital of Zhengzhou Yihe Hospital, Zhengzhou, Henan 450000, P.R. China, Second Hospital Affiliated to Xi'an Medical School, Xi'an, Shaanxi 710000, P.R. China, The Hypertension Institute of Fujian Province, Fuzhou, Fujian 350000, P.R. China
Published online on: July 3, 2014 https://doi.org/10.3892/ijmm.2014.1834
Pages: 828-834

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Abstract

The aim of this study was to investigate the inhibition capacity of telmisartan to endothelial inflammation induced by homocysteine (Hcy) and discuss the proposed mechanism in vitro. Human umbilical vein endothelial cells (HUVECs) were prepared by collagenase digestion and cultured in vitro. An increase in monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) as markers of Hcy-induced endothelial inflammation. HL-60 cell adhesion to HUVECs was measured by rose bengal staining. Nuclear, cytosolic and total nuclear transcription factor-κB (NF-κB) p65 levels were analyzed by western blotting. Peroxisome proliferator-activated receptor-δ (PPARδ) expression by HUVECs exposed to Hcy with or without telmisartan pretreatment was analyzed by RT-PCR and western blotting. Hcy significantly increased the levels of MCP-1 mRNA, VCAM-1 mRNA and monocyte binding to HUVECs. These effects were significantly attenuated by pretreatment with telmisartan and PPARδ agonists. The effect of telmisartan was inhibited by PPARδ antagonists. The Hcy-mediated downregulation of PPARδ mRNA and protein of HUVECs was inhibited by telmisartan. Hcy-mediated upregulation of NF-κB p65 protein levels in nuclear extracts was inhibited by telmisartan and PPARδ agonists. In conclusion, telmisartan exerts potent anti-inflammatory effects in endothelial cells, probably via a binary mechanism involving PPARδ activation and inhibition of the nuclear translocation of NF-κB.

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