Emodin Inhibits Homocysteine-Induced C-Reactive Protein Generation in Vascular Smooth Muscle Cells by Regulating PPARγ Expression and ROS-ERK1/2/p38 Signal Pathway.

Xiaoming Pang,Xiaolu Zhang,Yuxia Li,Juntian Liu,Jingjing Zhao,Utpal Sen

doi:10.1371/journal.pone.0131295

Xiaoming Pang, Xiaolu Zhang + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0131295

Copy DOI

Journal: PloS one	Publication Date: Jul 1, 2015
Citations: 27	License type: CC BY 4.0

Affiliation: Central Hospital of Zibo, Xi'an Jiaotong University

Abstract

Atherosclerosis is an inflammatory disease. As an inflammatory molecule, C-reactive protein (CRP) plays a direct role in atherogenesis. It is known that the elevated plasma homocysteine (Hcy) level is an independent risk factor for atherosclerosis. We previously reported that Hcy produces a pro-inflammatory effect by inducing CRP expression in vascular smooth muscle cells (VSMCs). In the present study, we observed effect of emodin on Hcy-induced CRP expression in rat VSMCs and molecular mechanisms. The in vitro results showed that pretreatment of VSMCs with emodin inhibited Hcy-induced mRNA and protein expression of CRP in a concentration-dependent manner. The in vivo experiments displayed that emodin not only inhibited CRP expression in the vessel walls in mRNA and protein levels, but also reduced the circulating CRP level in hyperhomocysteinemic rats. Further study revealed that emodin diminished Hcy-stimulated generation of reactive oxygen species (ROS), attenuated Hcy-activated phosphorylation of ERK1/2 and p38, and upregulated Hcy-inhibited expression of peroxisome proliferator-activated receptor gamma (PPARγ) in VSMCs. These demonstrate that emodin is able to inhibit Hcy-induced CRP generation in VSMCs, which is related to interfering with ROS-ERK1/2/p38 signal pathway and upregulating PPARγ expression. The present study provides new evidence for the anti-inflammatory and anti-atherosclerotic effects of emodin.

Highlights

Cardiovascular diseases resulting from atherosclerosis are the leading cause of mortality and morbidity all over the world
In order to choose the proper concentrations of emodin used for the in vitro study, effect of emodin on the viability of vascular smooth muscle cells (VSMCs) was observed
We previously reported that Hcy produces a pro-inflammatory effect on VSMCs by inducing C-reactive protein (CRP) expression [10]

Summary

Introduction

Cardiovascular diseases resulting from atherosclerosis are the leading cause of mortality and morbidity all over the world. Atherosclerosis is considered as a progressive narrowing of the artery lumen due to hyperlipidemia. Emodin Inhibits Homocysteine-Induced C-Reactive Protein Generation the recent years, a growing number of evidence from laboratory and clinical studies show that inflammation plays a pivotal role in all phases of atherogenesis, and support that atherosclerosis is a chronic inflammatory disease [2,3]. Among the various inflammatory molecules, C-reactive protein (CRP) is a representative inflammatory cytokine. An increasing number of data suggest that CRP directly participates in the initiation and progression of atherosclerosis through multiple activities in the inflammatory response [5]

Methods

Results

Discussion

Conclusion