M2 Macrophages as a Potential Target for Antiatherosclerosis Treatment

Atherosclerosis is a chronic progressive inflammation course, which could induce life-threatening diseases such as stroke and myocardial infarction. Optimal medical treatments for atherosclerotic risk factors with current antihypertensive and lipid-lowering drugs (for example, statins) are widely used in clinical practice. However, many patients with established disease still continue to have recurrent cardiovascular events in spite of treatment with a state-of-the-art therapy. Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality worldwide. Hence, current treatment of atherosclerosis is still far from being satisfactory. Recently, M2 macrophages have been found associated with atherosclerosis regression. The M2 phenotype can secrete anti-inflammatory factors such as IL-10 and TGF- β , promote tissue remodeling and repairing through collagen formation, and clear dying cells and debris by efferocytosis. Therefore, modulators targeting macrophages’ polarization to the M2 phenotype could be another promising treatment strategy for atherosclerosis. Two main signaling pathways, the Akt/mTORC/LXR pathway and the JAK/STAT6 pathway, are found playing important roles in M2 polarization. In addition, researchers have reported several potential approaches to modulate M2 polarization. Inhibiting or activating some kinds of enzymes, affecting transcription factors, or acting on several membrane receptors could regulate the polarization of the M2 phenotype. Besides, biomolecules, for example vitamin D, were found to affect the process of M2 polarization. Pomegranate juice could promote M2 polarization via unclear mechanism. In this review, we will discuss how M2 macrophages affect atherosclerosis regression, signal transduction in M2 polarization, and outline potential targets and compounds that affect M2 polarization, thus controlling the progress of atherosclerosis.