1. Academic Validation
  2. Ophiopogonin D and EETs ameliorate Ang II-induced inflammatory responses via activating PPARα in HUVECs

Ophiopogonin D and EETs ameliorate Ang II-induced inflammatory responses via activating PPARα in HUVECs

  • Biochem Biophys Res Commun. 2017 Aug 19;490(2):123-133. doi: 10.1016/j.bbrc.2017.06.007.
Xiaoyan Huang 1 Yuguang Wang 2 Zhaoyan Zhang 2 Yuan Wang 2 Xiangmei Chen 3 Yi Wang 4 Yue Gao 5
Affiliations

Affiliations

  • 1 Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
  • 2 Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
  • 3 Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, China.
  • 4 Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. Electronic address: vip_wangyi@126.com.
  • 5 Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China. Electronic address: gaoyue@nic.bmi.ac.cn.
Abstract

CYP2J2 is highly expressed in cardiovascular tissue including the heart and vascular endothelial cells. CYP2J2 and the EETs have been shown owning diverse biological effects. Our previous study found that ophiopogonin D (OP-D) suppressed drug-induced endoplasmic reticulum (ER) stress by upregulating the levels of CYP2J3/EETs in cardiomyocytes. The aim of this research was to investigate whether CYP2J2/EETs-PPARα pathway involved in endothelium protective effects of OP-D in human umbilical vein endothelial cells (HUVECs). The results showed that OP-D significantly inhibited Ang II induced NF-κB nuclear translocation, IκBα down-regulation and activation of pro-inflammatory cytokines (TNF-α, IL-6 and VCAM-1) by increasing the expression of CYP2J2/EETs and PPARα in HUVECs. Furthermore, treatment with exogenous 11,12-EET attenuated endothelial inflammation induced by Ang II as evidenced by inhibited NF-κB nuclear translocation, increased IκBα expression and decreased inflammation factor level. Finally, the activation of NF-κB nuclear translocation induced by Ang II was also markedly suppressed by fenofibrate. Co-incubation with 6-(2-proparglyloxyphenyl) hexanoic acid (PPOH) and PPARα Inhibitor GW6471 before drug treatment abolished the endothelium protective effects of OP-D. Taken together, these data suggest that OP-D has the endothelial protective effect through activation of CYP2J and increasing EETs, and PPARα involves in this process.

Keywords

Angiotensin II; CYP2J2; HUVECs; Ophiopogonin D; PPARα.

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