Macrophage phenotypic plasticity in atherosclerosis: The associated features and the peculiarities of the expression of inflammatory genes

•In atherosclerotic lesions macrophages demonstrate phenotypic plasticity.•Plaque macrophages rapidly adjust to changing microenvironmental conditions.•Overlapping set of transcription factors drives macrophage polarization.

Macrophages are essential players in induction and progression of atherosclerotic inflammation. The complexity of macrophage phenotypes was observed in human plaques and atherosclerotic lesions in mouse models of atherosclerosis. Plaque macrophages were shown to exhibit a phenotypic range that is intermediate between two extremes, M1 (pro-inflammatory) and M2 (anti-inflammatory). Indeed, in atherosclerosis, macrophages demonstrate phenotypic plasticity to rapidly adjust to changing microenvironmental conditions. In the plaque, serum lipids, serum lipoproteins and various pro- or anti-inflammatory stimuli such as cytokines, chemokines and small bioactive molecules could greatly influence the macrophage phenotype inducing switch towards more proinflammatory or anti-inflammatory properties. Dynamic plasticity of macrophages is achieved by up-regulation and down-regulation of an overlapping set of transcription factors that drive macrophage polarization. Understanding of mechanisms of macrophage plasticity and resolving functional characteristics of distinct macrophage phenotypes should help in the development of new strategies for treatment of chronic inflammation in atherosclerosis and other cardiovascular diseases.

Graphical abstractPlaque macrophages were shown to exhibit a phenotypic range that is intermediate between two extremes, M1 (proinflammatory) and M2 (anti-inflammatory). Complex signaling mechanisms mediating macrophage polarization towards the inflammatory or anti-inflammatory phenotype (Figure).Understanding of mechanisms of macrophage plasticity and resolving functional characteristics of distinct macrophage phenotypes should help in the development of new strategies for treatment of chronic inflammation in atherosclerosis.Download high-res image (166KB)Download full-size image