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

C-reactive protein (CRP) is a prototypic human acute phase reactant composed of five identical subunits. Emerging evidence indicates that CRP is not merely a predictor of cardiovascular disease, but may also be a direct mediator. However, the diverse and sometimes contradictory activities of CRP have considerably hampered the attempts to define the exact role of CRP in atherogenesis. Here, we review the multiple layers of regulation of CRP's structure and function, highlighting how local inflammation conditions, such as the abundance of damaged cell membranes and redox homeostasis, can tip the balance of the pro- and anti-inflammatory activities of CRP. We propose that the highly controlled interplay between different structural conformations of CRP underlies its intrinsic property as a fine modulator of inflammation and atherogenesis.