The Evolving Role of C-Reactive Protein in Atherothrombosis

Abstract

Background: Inflammation is pivotal in all phases of atherosclerosis. Among the numerous inflammatory biomarkers, the largest amount of published data supports a role for C-reactive protein (CRP) as a robust and independent risk marker in the prediction of primary and secondary adverse cardiovascular events. In addition to being a risk marker, there is much evidence indicating that CRP may indeed participate in atherogenesis. Content: In this review, we focus on the role of CRP in promoting atherothrombosis by discussing its effects on endothelial cells, endothelial progenitor cells, monocyte-macrophages, and smooth muscle cells. Conclusions: CRP is clearly a risk marker for cardiovascular disease and is recommended for use in primary prevention. In addition, CRP appears also to contribute to atherogenesis. However, much further research is needed, especially in appropriate animal models, to confirm the possible role of CRP in promoting atherothrombosis.

Pre-operative serum C-reactive protein as independent prognostic factor for survival but not infection in patients with high-grade osteosarcoma

“…Thus, the measurement of circulating serum CRP is an important monitor of inflammatory disease in clinical routine [13]. Moreover, there is a rapidly increasing body of evidence that CRP levels can also be elevated in patients with chronic infections, artherosclerosis or malignant disease when compared to healthy controls [14][15][16][17][18]. Additionally, it has been shown that in many cancer types overall survival is strongly linked to and can reliably be predicted by pre-operative serum CRP levels [19].…”

C-Reactive Protein is not an Independent Risk Factor for Ventricular Thrombus

“…2 Synthesis and secretion of CRP via paracrine and autocrine pathways by cells of the atherosclerotic region results in CRP concentrations exceeding greatly the concentrations in plasma enhancing proinflammatory and proatherogenic effects. But the assumed prothrombogenic effects of CRP has been less well evaluated.…”

“…It is a pentraxin type of protein comprising of 5 noncovalently associated protomers arranged symmetrically around a central pore with a moleculat weight of 118000 Daltons. 2 Its gene has been mapped to chromosome 1. Its role is in clearing necrotic cells.…”

“…3 It is transcriptionally driven by interleukin-6 and enhanced by interleukin-1. 2 CRP promotes innate immunity by binding complement factor C1q to activate the classical complement pathway. 4 Elevated CRP levels have been found to correlate with higher risk for future adverse cardiac events in patients with acute myocardial infarction 5,6 stable and unstable coronary artery disease.…”

Regulated conformation changes in C-reactive protein orchestrate its role in atherogenesis

“…Moreover, CRP co-localizes with atherogenic mediators, including modified low density lipoproteins (LDL) [22,23], activated complement [24] and foam cells [20]. Together with the reported pro-inflammatory actions of CRP [25,26], including activation of complement and stimulation of expression of cytokines and adhesion molecules in endothelial cells, this protein is emerging as a promising drug target for CVD treatment [16]. Accordingly, a small molecule inhibitor that blocks the ligand binding site on CRP significantly reduced the complement-dependent infarction size in a rat model [27].…”