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. 2024 Dec 18;21(1):51.
doi: 10.1186/s12950-024-00420-y.

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

Hanieh Gholamalizadeh  1 , Behzad Ensan  1 , Sercan Karav  2 , Tannaz Jamialahmadi  3   4 , Amirhossein Sahebkar  5   6   7
Affiliations

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

Hanieh Gholamalizadeh et al. J Inflamm (Lond). .

Abstract

Background: HMG-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.

Method: Scopus 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.

Results: The 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.

Conclusion: CCL2 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.

Keywords: CCL2; Ischemic heart disease; MCP-1; Statins; Stroke.

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Conflict of interest statement

Declarations. Ethical approval: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The CCL2/CCR2 axis plays a crucial role in the pathogenesis of atherosclerosis. Statins significantly interfere with the development and progression of atherosclerotic lesions by modulating the CCL2/CCR2 pathway as depicted(inspired by [209]). This figure shows how statins interfere with the migration of monocytes into the subendothelial layer, the production of collagen by smooth muscle cells (SMCs), lipid accumulation, and instability of developed plaques
Fig. 2
Fig. 2
Atherosclerosis results in many fatal clinical complications such as myocardial infarction, stroke, and aneurysm. Regulation of CCL2/CCR2 pathways is suggested as a possible therapeutic approach. Statins exert a part of their pleiotropic effect by modulating the CCL2/CCR2 axis. This figure explains how statins exert their protective effect on the catastrophic consequences of atherosclerosis based on in vitro and in vivo investigations. Increased adipose tissue is associated with higher levels of CCL-2. Statins showed promising results in down-regulating CCL2 and other inflammatory markers in adipocytes; the cells whose contribution to the atherosclerosis process is established. Red arrows depict how statins intervene in the pathogenesis of atherosclerosis complications based on in vitro and in vivo models
See this image and copyright information in PMC

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