The Clinical Significance and Potential Role of C-Reactive Protein in Chronic Inflammatory and Neurodegenerative Diseases

Abstract

C-reactive protein (CRP) is an acute-phase protein synthesized by hepatocytes in response to pro-inflammatory cytokines during inflammatory/infectious processes. CRP exists in conformationally distinct forms such as the native pentameric CRP and monomeric CRP (mCRP) and may bind to distinct receptors and lipid rafts and exhibit different functional properties. It is known as a biomarker of acute inflammation, but many large-scale prospective studies demonstrate that CRP is also known to be associated with chronic inflammation. This review is focused on discussing the clinical significance of CRP in chronic inflammatory and neurodegenerative diseases, such as cardiovascular disease, type 2 diabetes mellitus, age-related macular degeneration, hemorrhagic stroke, Alzheimer's disease, and Parkinson's disease, including recent advances on the implication of CRP and its forms specifically on the pathogenesis of these diseases. Overall, we highlight the advances in these areas that may be translated into promising measures for the diagnosis and treatment of inflammatory diseases.

Keywords: C-reactive protein; biomarker; cardiovascular disease; chronic inflammation; diabetes.

Figure 1

The potential mechanism underlying the role of CRP in the pathogenesis of CVDs. CRP may be involved in various stages through its direct influence on pathophysiological processes such as the activation of endothelial cells and macrophages, inhibition of apoptosis of neutrophils and expression of endothelial NO synthase, stimulation of the complement cascade, enhancement of PAI-1 activity and LDL uptake, accumulation of lipid and thrombosis, and upregulation of pro-inflammatory cytokine expression. Abbreviations: DIC, disseminated intravascular coagulation; LDL, low-density lipoprotein; CVD, cardiovascular diseases; TG, triglyceride; MCP-1, monocyte chemoattractant protein 1; ICAM-1, intercellular adhesion molecule 1; VCAM-1, vascular cell adhesion molecule 1; NO, nitric oxide; PI3K, phosphatidylinositol 3-kinase; ERK, extracellular signal-regulated kinase; MAPK, mitogen-activated protein kinase; PAI-1, plasminogen activator inhibitor-1; TGF-β, transforming growth factor-β; CRP, C-reactive protein.