M2 Macrophages as a Potential Target for Antiatherosclerosis Treatment

Abstract

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.

Araloside C attenuates atherosclerosis by modulating macrophage polarization via Sirt1-mediated autophagy

“…In past decades, research on antiatherosclerosis drugs mainly focused on lipid-reducing, anti-inflammatory, and antioxidative strategies, endothelial protection and foam cell inhibition. Few studies have focused on macrophage polarization, which is also a promising target for atherosclerosis therapy [37,38]. Generally, the anti-inflammatory macrophage phenotype is considered atheroprotective, although CD163 + macrophages promote atherosclerosis [3,4].…”

Beneficial Effects of Melatonin on Apolipoprotein-E Knockout Mice by Morphological and 18F-FDG PET/CT Assessments

“…Both of these populations are plastic cells because they can switch from the M1 to M2 state and vice versa upon specific signals; the changes from M1 to M2 has been defined as "macrophage polarization" [28]. Furthermore, M1 macrophages exhibit elevated lipid accumulation, which contribute to the acceleration of atherosclerosis; whereas in contrast, M2 macrophages are located far from the lipid core of the plaque, contain smaller lipid droplets, and are involved in phagocytosis [29][30][31]. In particular, Chinetti et al showed that in the adventitia, M2 macrophages are twofold to threefold more abundant than M1 macrophages [29].…”

Macrophage Modification Strategies for Efficient Cell Therapy

“…The opposite strategy of forcing macrophages into M2 phenotypes may be applied for the treatment of atherosclerosis [ 28 ]. LAIR1 (CD305) is an inhibitory collagen receptor expressed by certain blood cells, e.g., by monocytes.…”