Effect of C-reactive protein on vascular cells: evidence for a proinflammatory, proatherogenic role.
OBJECTIVE
C-reactive protein (CRP) is the prototypic downstream marker of inflammation. High levels of CRP predict future cardiovascular risk in apparently healthy men and women. Recent evidence from different cell types suggests that CRP is not only a risk marker but may also be a participant in atherogenesis. This review will focus on the effects of CRP on different cells involved in atherosclerosis.


RESULTS
CRP is shown to induce matrix metalloproteinase-1 (MMP-1) expression through the Fc gamma RII and extracellular signal-related kinase pathway in U937 cells. MMPs are implicated in plaque instability. A recent report shows that CRP does not induce tissue factor in human monocytes directly, disputing the previous concept that CRP induces tissue factor in monocytes. CRP is shown to upregulate interleukin-8 in human aortic endothelial cells via nuclear factor-kappa B. CRP promotes monocyte chemoattractant protein-1-mediated chemotaxis by upregulating CC-chemokine receptor 2 expression in human monocytes. Also CRP is shown to attenuate endothelial progenitor cell survival, differentiation, and function via inhibiting nitric oxide. Human CRP transgenic animal models show that CRP promotes atherothrombosis and increases plasminogen activator inhibitor-1. Also, the classic dogma that CRP is produced exclusively in liver is challenged by recent data on the extrahepatic production of CRP in different cells including atherosclerotic lesions.


CONCLUSIONS
All this recent evidence along with earlier reports support a role for CRP in atherosclerosis.
Venugopal
Senthil Kumar
SK
Laboratory for Atherosclerosis and Metabolic Research, UC Davis Medical Center, Sacramento, CA 95817, USA. skvenugopal@ucdavis.edu
Devaraj
Sridevi
S
Jialal
Ishwarlal
I
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism / Q000503:physiopathology*; D002097:C-Reactive Protein / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology*; D012307:Risk Factors; D015854:Up-Regulation
D002097:C-Reactive Protein