title: Chemokines and atherosclerosis: focus on the CX3CL1/CX3CR1 pathway.
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.
authors: Department of Clinical Virology, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.
authors: Stavros
authors: S
authors: Apostolakis
authors: Demetrios
authors: D
authors: Spandidos
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000503:physiopathology*; D015415:Biomarkers / Q000378:metabolism; D054428:Chemokine CX3CL1 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D017720:Molecular Epidemiology; D011379:Prognosis; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D018836:Inflammation Mediators
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