Chemokines and atherosclerosis: focus on the CX3CL1/CX3CR1 pathway

Acta Pharmacol Sin. 2013 Oct;34(10):1251-6. doi: 10.1038/aps.2013.92. Epub 2013 Aug 26.

Abstract

Atherosclerosis is currently considered an inflammatory disease. Much attention has been focused on the potential role of inflammatory mediators as prognostic/diagnostic markers or therapeutic targets of atherosclerotic cardiovascular disease. CX3CL1 (or fractalkine) is a structurally and functionally unique chemokine with a well documented role in atherosclerosis. In its membrane bound form it promotes the firm adhesion of rolling leucocytes onto the vessel wall, while in its soluble form it serves as a potent chemoattractant for CX3CR1-expressing cells. Additionally, CX3CL1 exerts cytotoxic effects on the endothelium as well as anti-apoptotic and proliferative effects on vascular cells, affecting the context and stability of the atherosclerotic plaque. Studies on animal models have shown that the blockade of the CX3CL1/CX3CR1 pathway ameliorates the severity of atherosclerosis, while genetic epidemiology has confirmed that a genetically-defined less active CX3CL1/CX3CR1 pathway is associated with a reduced risk of atherosclerotic disease in humans. Although several studies support an important pathogenic role of CX3CL1/CX3CR1 in atherogenesis and plaque destabilization, this does not necessarily suggest that this pathway is a suitable therapeutic target or that CX3CL1 can serve as a prognostic/diagnostic biomarker. Further studies on the CX3CL1/CX3CR1 chemokine pathway are clearly warranted to justify the clinical relevance of its role in atherosclerosis.

Publication types

  • Review

MeSH terms

  • Animals
  • Atherosclerosis / genetics
  • Atherosclerosis / physiopathology*
  • Biomarkers / metabolism
  • Chemokine CX3CL1 / genetics
  • Chemokine CX3CL1 / metabolism*
  • Disease Models, Animal
  • Genetic Predisposition to Disease
  • Humans
  • Inflammation Mediators / metabolism
  • Molecular Epidemiology
  • Prognosis
  • Severity of Illness Index

Substances

  • Biomarkers
  • CX3CL1 protein, human
  • Chemokine CX3CL1
  • Inflammation Mediators