A role for monomeric C-reactive protein in regulation of angiogenesis, endothelial cell inflammation and thrombus formation in cardiovascular/cerebrovascular disease?

Abstract

Native CRP (nCRP) is a pentameric oligoprotein composed of identical 23 KDa subunits which can be irreversibly dissociated to form free subunits or monomeric CRP (mCRP). mCRP has a reduced aqueous solubility and a tendency to aggregate into matrix-like lattices in various tissues, in particular, blood vessel walls. A dramatic increase in expression of mCRP occurs in angiogenic blood vessels derived from stroked brain regions, atherosclerotic arteries and active vessels from other angiogenic diseases such as Alzheimer’s. Furthermore, mCRP unlike the native molecule is highly angiogenic to vascular endothelial cells in vitro and therefore might impact on the processes of vascularization and re-modelling thus affecting tissue survival and development. In this mini-review, we will discuss the differences in the biological properties between nCRP and mCRP. We will provide a brief historical background to the importance of nCRP as a biomarker for cardiovascular disease. We will explain the mechanisms of conversion of nCRP to its monomeric form and describe evidence for the role of mCRP in modulation of endothelial cell activation, promotion of inflammatory status and thrombus formation in cardio/cerebrovascular disease. Finally, we will provide evidence for the accumulation of mCRP in angiogenic microvessels from diseased tissue, and demonstrate its highly pro-angiogenic capabilities. The discovery of the existence of this tissue-associated, highly angiogenic monomeric form of CRP capable of cellular binding and intra-cellular signal transduction activation may help in our understanding of the processes responsible for modulation of angiogenesis and inflammation in disease.