Regulatory impact of statins on macrophage polarization: mechanistic and therapeutic implications.

Statins, also known as HMG-CoA reductase inhibitors, are widely prescribed drugs for the prevention and treatment of cardiovascular diseases. In addition to their lipid-lowering effects, these compounds have been found to possess immune-modulating properties. Macrophages, which are crucial phagocytic cells in the body, can be divided into two main subsets: M1 (proinflammatory) and M2 (anti-inflammatory). While there is evidence suggesting that statins exert an anti-inflammatory action on macrophages and promote their polarization towards the M2 subset, recent studies have identified the proinflammatory impact of statins on macrophages, leading to polarization towards the M1 subset. For example, statins have been shown to inhibit NF-κB activation to promote anti-inflammatory responses. On the other hand, statins can induce NFκB/AP-1 activation and increase IL-1ß secretion in macrophages to promote pro-inflammatory responses. This review aims to provide a comprehensive overview of both in vivo and in vitro studies that have investigated the effects of statins on macrophage polarization and inflammatory responses in various diseases. Furthermore, this review seeks to evaluate the underlying mechanisms involved in these effects. By summarizing the existing evidence, this review contributes to our understanding of the complex interactions between statins and macrophages in different disease contexts.

The potential role of miRNA in regulating macrophage polarization.

Macrophage polarization is a dynamic process determining the outcome of various physiological and pathological situations through inducing pro-inflammatory responses or resolving inflammation via exerting anti-inflammatory effects. The miRNAs are epigenetic regulators of different biologic pathways that target transcription factors and signaling molecules to promote macrophage phenotype transition and regulate immune responses. Modulating the macrophage activation, differentiation, and polarization by miRNAs is crucial for immune responses in response to microenvironmental signals and under various physiological and pathological conditions. In term of clinical significance, regulating macrophage polarization via miRNAs could be utilized for inflammation control. Also, understanding the role of miRNAs in macrophage polarization can provide insights into diagnostic strategies associated with dysregulated miRNAs and for developing macrophage-centered therapeutic methods. In this case, targeting miRNAs to further regulate of macrophage polarization may become an efficient strategy for treating immune-associated disorders. The current review investigated and categorized various miRNAs directly or indirectly involved in macrophage polarization by targeting different transcription factors and signaling pathways. In addition, prospects for regulating macrophage polarization via miRNA as a therapeutic choice that could be implicated in various pathological conditions, including cancer or inflammation-mediated injuries, were discussed.