Monomeric C-Reactive Protein in Atherosclerotic Cardiovascular Disease: Advances and Perspectives

Abstract

This review aimed to trace the inflammatory pathway from the NLRP3 inflammasome to monomeric C-reactive protein (mCRP) in atherosclerotic cardiovascular disease. CRP is the final product of the interleukin (IL)-1β/IL-6/CRP axis. Its monomeric form can be produced at sites of local inflammation through the dissociation of pentameric CRP and, to some extent, local synthesis. mCRP has a distinct proinflammatory profile. In vitro and animal-model studies have suggested a role for mCRP in: platelet activation, adhesion, and aggregation; endothelial activation; leukocyte recruitment and polarization; foam-cell formation; and neovascularization. mCRP has been shown to deposit in atherosclerotic plaques and damaged tissues. In recent years, the first published papers have reported the development and application of mCRP assays. Principally, these studies demonstrated the feasibility of measuring mCRP levels. With recent advances in detection techniques and the introduction of first assays, mCRP-level measurement should become more accessible and widely used. To date, anti-inflammatory therapy in atherosclerosis has targeted the NLRP3 inflammasome and upstream links of the IL-1β/IL-6/CRP axis. Large clinical trials have provided sufficient evidence to support this strategy. However, few compounds target CRP. Studies on these agents are limited to animal models or small clinical trials.

Keywords: C-reactive protein; atherosclerosis; biomarker; inflammation; mCRP; monomeric C-reactive protein; residual inflammatory risk; thromboinflammation.

Figure 1

Proposed roles for mCRP in atherosclerosis. mCRP, monomeric C-reactive protein; pCRP, pentameric C-reactive protein; TF, tissue factor; CAM, cell-adhesion molecules; oxLDL, oxidized low-density lipoproteins.

Figure 2

Anti-inflammatory agents targeting the NLRP3 inflammasome and IL-1β/IL-6/CRP axis. Upstream agents targeting the NLRP3 inflammasome, interleukin (IL)-1β, and IL-6 reduce the rate of major adverse cardiovascular events, according to large RCTs. Downstream agents target translation of pCRP in the liver, CRP dissociation, and mCRP. Studies on these agents are limited to animal models and small RCTs. CRP, C-reactive protein; mCRP, monomeric C-reactive protein; pCRP, pentameric C-reactive protein; RCTs, randomized clinical trials.