The Multiple Faces of C-Reactive Protein-Physiological and Pathophysiological Implications in Cardiovascular Disease

Abstract

C-reactive protein (CRP) is an intriguing protein which plays a variety of roles in either physiological or pathophysiological states. For years it has been regarded merely as a useful biomarker of infection, tissue injury and inflammation, and it was only in the early 80s that the modified isoforms (mCRP) of native CRP (nCRP) appeared. It soon became clear that the roles of native CRP should be clearly discriminated from those of the modified form and so the impacts of both isoforms were divided to a certain degree between physiological and pathophysiological states. For decades, CRP has been regarded only as a hallmark of inflammation; however, it has since been recognised as a significant predictor of future episodes of cardiovascular disease, independent of other risk factors. The existence of modified CRP isoforms and their possible relevance to various pathophysiological conditions, suggested over thirty years ago, has prompted the search for structural and functional dissimilarities between the pentameric nCRP and monomeric mCRP isoforms. New attempts to identify the possible relevance between the diversity of structures and their opposing functions have initiated a new era of research on C-reactive protein. This review discusses the biochemical aspects of CRP physiology, emphasizing the supposed relevance between the structural biology of CRP isoforms and their differentiated physiological and pathophysiological roles.

Keywords: C-reactive protein; cardio-vascular disease; inflammation; monomeric CRP; protein conformation.

Figure 1

Possible interactions of CRP with blood cells and plasma components. Pentameric CRP (nCRP) bound to microbial polysaccharides or ligands exposed on damaged cells activates the classical complement pathway through the interaction with C1q. Both pro-and anti-inflammatory effects are attributed to nCRP via its interactions with blood cells (for details, please see Section 3). At the site of the injured endothelium, circulating platelets undergo activation and spread. On the surface of the activated platelets, circulating cell-derived microparticles and apoptotic cell membranes, pentameric CRP dissociates to monomeric CRP (mCRP), which exerts pro-inflammatory effects by activating blood cells and by promoting inflammatory response. mCRP can be deposited in atherosclerotic lesions.