Requirements for the binding of C‐reactive protein to oxidized low‐density lipoprotein

Abstract

We are investigating the interactions between C‐reactive protein (CRP) and various forms of low‐density lipoprotein (LDL). Previously, we reported that phosphoethanolamine (PEt)‐complexed CRP, but not free CRP, bound to native LDL and that PEt‐complexed CRP was more potent than free CRP in binding to enzymatically‐modified LDL (E‐LDL). In this study, we explored the binding of CRP to oxidized LDL (oxLDL). In an ELISA‐based solid‐phase binding assay, freshly‐purified native CRP did not bind to immobilized oxLDL. Interestingly, in the presence of PEt, freshly‐purified native CRP bound to immobilized oxLDL efficiently in a dose‐dependent manner. In contrast, when an old preparation of frozen CRP was thawed and used in the assay, CRP bound to oxLDL even in the absence of PEt and the binding was dramatically enhanced in the presence of PEt. The mechanism of action of PEt in the binding of CRP to various forms of LDL is not known, but it is reasonable to assume that PEt modifies CRP in a way similar to storage‐induced modification of CRP. Defining the requirements for the binding of CRP to various forms of LDL is important because, by binding to LDL, CRP can prevent formation of LDL‐loaded macrophage foam cells. As shown previously by using CRP‐E‐LDL complexes, CRP‐bound E‐LDL does not cause formation of foam cells which is one of the processes that contribute to the development of atherosclerosis. NIH R01HL071233