Does C-Reactive Protein Contribute to Atherothrombosis Via Oxidant-Mediated Release of Pro-Thrombotic Factors and Activation of Platelets?

Zhuo Zhang,Jianbo Wu,Yan Yang,Michael A Hill

doi:10.3389/fphys.2012.00433

Abstract

Inflammation and the generation of reactive oxygen species (ROS) have been implicated in the initiation and progression of atherosclerosis. Although C-reactive protein (CRP) has traditionally been considered to be a biomarker of inflammation, recent in vitro and in vivo studies have provided evidence that CRP, itself, exerts pro-thrombotic effects on vascular cells and may thus play a critical role in the development of atherothrombosis. Of particular importance is that CRP interacts with Fcγ receptors on cells of the vascular wall giving rise to the release of pro-thrombotic factors. The present review focuses on distinct sources of CRP-mediated ROS generation as well as the pivotal role of ROS in CRP-induced tissue factor expression. These studies provide considerable insight into the role of the oxidative mechanisms in CRP-mediated stimulation of pro-thrombotic factors and activation of platelets. Collectively, the available data provide strong support for ROS playing an important intermediary role in the relationship between CRP and atherothrombosis.

Highlights

Mounting evidence indicates that atherosclerosis is a chronic inflammatory process, and further, that inflammation plays an important role in acute coronary syndromes (Davì and Patrono, 2007)
There appears to be a complex interplay between reactive oxygen species (ROS) and other inflammatory mediators, such as C-reactive protein (CRP) (Zeller and Sullivan, 1992; Irani, 2000; Venugopal et al, 2003; Qamirani et al, 2005; Ryu et al, 2007; Singh et al, 2007; Wu et al, 2008), whereby ROS induce production of the inflammatory mediator, but are produced in response to the mediator
ROS generation plays a significant role in inflammatory processes, and the subsequent activation of prothrombotic factors and platelets by inflammatory mediators may be a critical component of atherothrombosis

Summary

Introduction

Mounting evidence indicates that atherosclerosis is a chronic inflammatory process, and further, that inflammation plays an important role in acute coronary syndromes (Davì and Patrono, 2007). ROS generation triggers a cascade of events including inflammation, endothelial cell injury, blood coagulation, and thrombosis.

Results

Conclusion