Regulatory effects of statins on CCL2/CCR2 axis in cardiovascular diseases: new insight into pleiotropic effects of statins

BackgroundHMG-CoA reductase inhibitors are well-known medications in the treatment of cardiovascular disorders due to their pleiotropic and lipid-lowering properties. Herein, we reviewed the effects of statins on the CCL2/CCR2 axis.MethodScopus and Pubmed databases were systematically searched using the following keywords: Hydroxymethylglutaryl CoA Reductase Inhibitors, HMG-CoA Reductase Inhibitors, Statins, CCL2, Chemokine, Monocyte Chemoattractant Protein-1 and Chemokine (C-C Motif) Ligand 2. Evidence investigating the role of statin on MCP-1 in CVD was identified and bibliographies were completely evaluated to gather further related studies.ResultsThe anti-inflammatory effects of statins on the CCL2/CCR2 pathway have been widely investigated. Despite inconclusive results, a great body of research supports the regulatory roles of statins on this pathway due to their pleiotropic effects. By disrupting the CCL2/CCR2 axis, statins attenuate the infiltration of monocytes and macrophages into the zone of inflammation and hence down-regulate the inflammatory cascades in various CVDs including atherosclerosis, cardiac remodeling, and stroke, among others.ConclusionCCL2 plays a major role in the pathogenesis of cardiovascular disorders. Down-regulation of CCL2 is proposed as one of the pleiotropic properties of statins. However, more investigations are required to elucidate which statin in what dose exerts a more potent effect on CCL2/CCR2 pathway.