Metabolic and epigenetic regulation of macrophage polarization in atherosclerosis: Molecular mechanisms and targeted therapies
Pinglian Yang, Xiaoling Rong, Zhechang Gao, Jiaojiao Wang, Zhiping Liu
Abstract
Atherosclerosis, a multifactorial progressive inflammatory disease, is the common pathology underlying cardiovascular and cerebrovascular diseases. The macrophage plasticity is involved in the pathogenesis of atherosclerosis. With the advance of metabolomics and epigenetics, metabolites/metabolic and epigenetic modification such as DNA methylation, histone modification and noncoding RNA, play a crucial role in macrophage polarization and the progression of atherosclerosis. Herein, we provide a comprehensive review of the essential role of metabolic and epigenetic regulation, as well as the crosstalk between the two in regulating macrophage polarization in atherosclerosis. We also highlight the potential therapeutic strategies of regulating macrophage polarization via epigenetic and metabolic modifications for atherosclerosis, and offer recommendations to advance our knowledge of the roles of metabolic-epigenetic crosstalk in macrophage polarization in the context of atherosclerosis. Fundamental studies that elucidate the mechanisms by which metabolic and epigenetic regulation of macrophage polarization influence atherosclerosis will pave the way for novel therapeutic approaches. Macrophage polarization is critical for the progression and regression of atherosclerosis. Macrophage polarization is orchestrated by epigenetic modifications, such as DNA methylation, RNA methylation, non-coding RNAs, histone modification. Besides, metabolic regulation and metabolic-epigenetic crosstalk are also implicated in controlling macrophage polarization. The fate of atherosclerosis is determined by the unique profile of macrophages, which consists primarily of glycolytic-characterized M1 macrophages (pro-inflammation) and OXPHOS-characterized M2 macrophages (anti-inflammation).