C-Reactive Protein in Atherothrombosis and Angiogenesis

Abstract

C-reactive protein (CRP) is a short pentraxin mainly found as a pentamer in the circulation, or as non-soluble monomers CRP (mCRP) in tissues, exerting different functions. This review is focused on discussing the role of CRP in cardiovascular disease, including recent advances on the implication of CRP and its forms specifically on the pathogenesis of atherothrombosis and angiogenesis. Besides its role in the humoral innate immune response, CRP contributes to cardiovascular disease progression by recognizing and binding multiple intrinsic ligands. mCRP is not present in the healthy vessel wall but it becomes detectable in the early stages of atherogenesis and accumulates during the progression of atherosclerosis. CRP inhibits endothelial nitric oxide production and contributes to plaque instability by increasing endothelial cell adhesion molecules expression, by promoting monocyte recruitment into the atheromatous plaque and by enzymatically binding to modified low-density lipoprotein. CRP also contributes to thrombosis, but depending on its form it elicits different actions. Pentameric CRP has no involvement in thrombogenesis, whereas mCRP induces platelet activation and thrombus growth. In addition, mCRP has apparently contradictory pro-angiogenic and anti-angiogenic effects determining tissue remodeling in the atherosclerotic plaque and in infarcted tissues. Overall, CRP contributes to cardiovascular disease by several mechanisms that deserve an in-depth analysis.

Keywords: angiogenesis; atherosclerosis; c-reactive protein; cardiovascular disease; ischemic heart disease; monomeric C-reactive protein; pentameric C-reactive protein; thrombosis.

Figure 1

Involvement of C-reactive protein (CRP) in atherothrombosis. CRP contributes to the development and progression of atherosclerosis and thrombosis by several mechanisms that induce endothelial dysfunction, leukocyte recruitment at atherosclerotic lesions, and thrombus formation through platelet activation and aggregation.

Figure 2

Implications of C-reactive protein (CRP) in angiogenesis. monomeric CRP (mCRP) has apparently contradictory pro-angiogenic and anti-angiogenic effects which determine tissue remodeling in the atherosclerotic plaque and in infarcted tissues.