C-reactive protein: from innocent bystander to pivotal mediator of atherosclerosis.
There is compelling evidence that C-reactive protein is a sensitive marker for the development of cardiovascular disease in the general population. Recent studies suggest that C-reactive protein is not only a biomarker but also an active mediator in the pathogenesis of atherosclerosis. We review the evidence and suggest mechanisms by which C-reactive protein can damage arterial endothelium and promote the development of atherosclerotic lesions, including the effects of C-reactive protein on arterial endothelial activation, macrophage recruitment, and foam cell generation. The direct role of C-reactive protein in sustaining a proinflammatory and procoagulant milieu within the arterial neointima is emphasized. We also discuss the evidence that C-reactive protein can injure arterial endothelium. Finally, we review therapies that target C-reactive protein for primary prevention and for the treatment of atherosclerotic diseases.
Methodist Research Institute, Clarian Health Partners, Inc., Indianapolis, Indiana 46202, USA. clabarrere@clarian.org
Carlos A
CA
Labarrere
Gary P
GP
Zaloga
D000210:Acute-Phase Reaction / Q000276:immunology; D001158:Arteries / Q000276:immunology; D001161:Arteriosclerosis / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000737:chemistry / Q000502:physiology*; D018925:Chemokines / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology; D005487:Foam Cells / Q000276:immunology; D006801:Humans; D007249:Inflammation; D018836:Inflammation Mediators / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D008991:Monitoring, Physiologic / Q000379:methods; D018579:Patient Selection; D011322:Primary Prevention; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013997:Time Factors
D015415:Biomarkers; D018925:Chemokines; D018836:Inflammation Mediators; D002097:C-Reactive Protein