Monomeric C-Reactive Protein: Current Perspectives for Utilization and Inclusion as a Prognostic Indicator and Therapeutic Target

Abstract

Monomeric C-reactive protein (mCRP), once thought to be a figment of the imagination and whose biological activity was ascribed to its sodium azide preservative, has now pronounced itself as a critical molecule playing a direct role in mediating many of the acute and chronic aberrant pathological responses to inflammation. In this focused mini review, we describe the currently attributed pathobiological interactions of mCRP in disease, where its tissue and cellular distribution and deposition have recently been clearly characterized and linked to inflammation and other pathway-associated progression of neurological and cardiovascular complications and deleterious outcomes. and focus upon current opinions as to the diagnostic and prognostic potential of mCRP-plasma circulating protein and define the possible future therapeutics including ongoing research attempting to block CRP dissociation with small molecule inhibitors or prevention of cell surface binding directly using antibodies or modified orphan drug targeting directed towards CRP, inhibiting its cellular interactions and signaling activation. There is no doubt that understanding the full influence of the biological power of mCRP in disease development and outcome will be considered a critical parameter in future stratified treatment.

Keywords: cardiovascular disease; diagnostic; monomeric C-reactive protein; neuropathology; therapeutic.

Figure 1

(A) Expression of native C‐reactive protein (nCRP) in contralateral brain tissue: almost no expression of nCRP was seen in blood vessels and neurons from normal looking brain tissue [arrows mark the blood vessels; 3,3′‐diaminobenzidine‐tetrachloride (DAB) brown development; Patient 17]. (B) Expression of nCRP in peri‐infarcted brain tissue again showing no notable expression, apart from occasional staining within the lumen of larger vessels (arrows; DAB brown development; Patient 17). (C) Expression of monomeric form of CRP (mCRP) in contralateral brain tissue: almost no expression of mCRP was seen in normal looking brain tissue (arrows mark the blood vessels; DAB brown development). mCRP was abundantly expressed in peri‐infarcted (D–F) and infarcted (G, H) brain tissue particularly in microvessels (marked by arrows; DAB brown development). Taken from Reference (16).