Transitional changes in the structure of C-reactive protein create highly pro-inflammatory molecules: Therapeutic implications for cardiovascular diseases

C-reactive protein (CRP) is the prototypic acute-phase reactant that has long been recognized almost exclusively as a marker of inflammation and predictor of cardiovascular risk. However, accumulating evidence indicates that CRP is also a direct pathogenic pro-inflammatory mediator in atherosclerosis and cardiovascular diseases. The 'CRP system' consists of at least two protein conformations with distinct pathophysiological functions. The bind-ing of the native, pentameric CRP (pCRP) to activated cell membranes leads to a conformational change resulting in two highly pro-inflammatory isoforms, pCRP* and monomeric CRP (mCRP). The deposition of these pro-inflammatory isoforms has been shown to aggravate the localized tissue injury in a broad range of pathological conditions including atherosclerosis and thrombosis, myocardial infarction, and stroke. Here, we review recent findings on how these structural changes contribute to the inflammatory response and discuss the transitional changes in the structure of CRP as a novel therapeutic target in cardiovascular diseases and overshooting inflam-mation.(c) 2022 Elsevier Inc. All rights reserved.

Automated summary

C-reactive protein (CRP) is not only a marker of inflammation and predictor of cardiovascular risk, but also a direct pathogenic pro-inflammatory mediator in atherosclerosis and cardiovascular diseases. The different conformations of the CRP system can aggravate tissue injury in pathological conditions, and studying the structural changes of CRP could be a novel therapeutic target for cardiovascular diseases and excessive inflammation.