Modified C-Reactive Protein is Expressed in Adventitia and Intimal Neovessels from Complicated Regions of Unstable Carotid Plaques

Abstract

Objective: Native C-reactive protein (nCRP) is a soluble acute phase reactant whose expression in the vascular wall; in particular, in reactive plaque regions, and circulating levels increase in patients with inflammatory disease. We have recently demonstrated a specific role for the insoluble, monomeric form of CRP (mCRP) in direct stimulation of an- giogenesis and therefore decided to investigate its expression in carotid adventitial vasa vasorum and plaque intimal neovessels to determine if it could be involved in the development of unstable plaque lesions. Methods: We have used immunohistochemistry to examine the expression of both mCRP and nCRP in a series of carotid arterial plaques obtained at transplant (n=20) and employed double immunoflourescent labelling to identify any associa- tion of CRP with active-CD105-positive microvessels. Results: Using characterised and specific antibodies we have identified strong expression of mCRP in adventitial vasa vasorum and angiogenic neovessels from unstable regions of complicated carotid plaques. mCRP was also found to be as- sociated with infiltrating macrophages in inflammatory regions but infrequently with vascular smooth muscle cells. nCRP was expressed much more weakly and only in some regions rich in inflammatory cells. Many of the mCRP-positive ves- sels also stained positive for CD105 suggesting they were actively involved in the process of angiogenesis. Conclusions: Based on our previously published observations of the highly angiogenic nature of mCRP in vitro, we hy- pothesise that mCRP is intimately involved in promotion of neovascularization and possibly, subsequent destabilization of atherosclerotic plaques and could be considered as a possible target for therapeutic manipulation of angiogenesis.