Atherosclerosis-Related Functions of C-Reactive Protein

Alok      Agrawal; David      J. Hammond; Sanjay      K. Singh

Abstract

C-reactive protein (CRP) is secreted by hepatocytes as a pentameric molecule made up of identical monomers, circulates in the plasma as pentamers, and localizes in atherosclerotic lesions. In some cases, localized CRP was detected by using monoclonal antibodies that did not react with native pentameric CRP but were specific for isolated monomeric CRP. It has been reported that, once CRP is bound to certain ligands, the pentameric structure of CRP is altered so that it can dissociate into monomers. Accordingly, the monomeric CRP found in atherosclerotic lesions may be a stationary, ligand-bound, by-product of a ligand-binding function of CRP. CRP binds to modified forms of low-density lipoprotein (LDL). The binding of CRP to oxidized LDL requires acidic pH conditions; the binding at physiological pH is controversial. The binding of CRP to enzymatically-modified LDL occurs at physiological pH; however, the binding is enhanced at acidic pH. Using enzymatically-modified LDL, CRP has been shown to prevent the formation of enzymatically-modified LDL-loaded macrophage foam cells. CRP is neither pro-atherogenic nor atheroprotective in ApoE-/- and ApoB100/100Ldlr -/- murine models of atherosclerosis, except in one study where CRP was found to be slightly atheroprotective in ApoB100/100Ldlr -/- mice. The reasons for the ineffectiveness of human CRP in murine models of atherosclerosis are not defined. It is possible that an inflammatory environment, such as those characterized by acidic pH, is needed for efficient interaction between CRP and atherogenic LDL during the development of atherosclerosis and to observe the possible atheroprotective function of CRP in animal models.

Keywords: Atherosclerosis, C-reactive protein, Enzymatically-modified low-density lipoprotein, Foam cells, Oxidized lowdensity lipoprotein, hepatocytes, lipoprotein, Enzymatically-modified, low-density lipoprotein, platelets, serum, cardiovascular disease, heat shock proteins, immunohistochemical, immunofluorescent, cholesteryl ester, pro-atherogenic, atheroprotective, mutagenesis, endotoxins, albumin, Enzymatically-modified LDL, Oxidized LDL