Chistiakov Dimitry A, Bobryshev Yuri V, Nikiforov Nikita G, Elizova Natalia V, Sobenin Igor A, Orekhov Alexander N
Department of Medical Nanobiotechnology, Pirogov Russian State Medical University, Moscow 117997, Russia.
Faculty of Medicine, School of Medical Sciences, University of New South Wales, NSW 2052, Sydney, Australia; Clinical School of Medicine, University of Western Sydney, Campbelltown, NSW 2560, Australia; Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow125315, Russia.
Int J Cardiol. 2015 Apr 1;184:436-445. doi: 10.1016/j.ijcard.2015.03.055. Epub 2015 Mar 5.
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.
巨噬细胞是动脉粥样硬化炎症诱导和进展过程中的关键参与者。在人类斑块以及动脉粥样硬化小鼠模型的动脉粥样硬化病变中，观察到了巨噬细胞表型的复杂性。斑块巨噬细胞表现出的表型范围介于两个极端之间，即M1（促炎）和M2（抗炎）。事实上，在动脉粥样硬化中，巨噬细胞表现出表型可塑性，能够快速适应不断变化的微环境条件。在斑块中，血清脂质、血清脂蛋白以及各种促炎或抗炎刺激物，如细胞因子、趋化因子和小生物活性分子，可极大地影响巨噬细胞表型，促使其向更具促炎或抗炎特性转变。巨噬细胞的动态可塑性是通过驱动巨噬细胞极化的一组重叠转录因子的上调和下调来实现的。了解巨噬细胞可塑性的机制并解析不同巨噬细胞表型的功能特征，应有助于开发治疗动脉粥样硬化和其他心血管疾病中慢性炎症的新策略。
