Macrophage Phenotype and Function in Different Stages of Atherosclerosis.
Macrophage Phenotype and Function in Different Stages of Atherosclerosis.
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DOI：
10.1161/circresaha.115.306256
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发表时间：
2016-02-19
影响因子：
20.1
通讯作者：
Bornfeldt KE
中科院分区：
文献类型：
--
作者：
Tabas I;Bornfeldt KE
50多年来，巨噬细胞显著的可塑性和过多的生物学功能吸引了科学家们研究这些细胞与动脉粥样硬化的关系，今天仍有重大发现。现已认识到巨噬细胞在动脉粥样硬化的各个阶段都发挥着重要作用，从病变的起始和病变的扩大，到坏死导致破裂和动脉粥样硬化的临床表现，再到动脉粥样硬化病变的消退和消退。皮损巨噬细胞主要来源于血液单核细胞，尽管最近的研究表明，皮损巨噬细胞样细胞也可以来源于平滑肌细胞。皮损巨噬细胞根据其所处的环境和激活的细胞内信号通路呈现不同的表型。与少数几种不同的巨噬细胞不同，病变巨噬细胞的表型更加复杂，可能在动脉粥样硬化的不同阶段以及随着脂质和胆固醇负荷的程度、过量受体的激活以及细胞的代谢状态而发生变化。这些不同的表型允许巨噬细胞吞噬脂类、死亡细胞和其他被视为危险信号的物质；将胆固醇排出到高密度脂蛋白；增殖和迁移；经历凋亡和死亡；并分泌大量炎症和促进分解的分子。这篇综述文章是动脉粥样硬化纲要的一部分，讨论了我们对动脉粥样硬化不同阶段病变巨噬细胞的表型和功能的了解的最新进展。随着对皮损巨噬细胞作用的认识日益加深，新的研究领域和治疗策略开始出现。
The remarkable plasticity and plethora of biological functions performed by macrophages have enticed scientists to study these cells in relation to atherosclerosis for more than 50 years, and major discoveries continue to be made today. It is now understood that macrophages play important roles in all stages of atherosclerosis, from initiation of lesions and lesion expansion, to necrosis leading to rupture and the clinical manifestations of atherosclerosis, to resolution and regression of atherosclerotic lesions. Lesional macrophages are derived primarily from blood monocytes, although recent research has shown that lesional macrophage-like cells can also be derived from smooth muscle cells. Lesional macrophages take on different phenotypes depending on their environment and which intracellular signaling pathways are activated. Rather than a few distinct populations of macrophages, the phenotype of the lesional macrophage is more complex and likely changes during the different phases of atherosclerosis and with the extent of lipid and cholesterol loading, activation by a plethora of receptors, and metabolic state of the cells. These different phenotypes allow the macrophage to engulf lipids, dead cells, and other substances perceived as danger signals; efflux cholesterol to HDL; proliferate and migrate; undergo apoptosis and death; and secrete a large number of inflammatory and pro-resolving molecules. This review article, part of the Compendium on Atherosclerosis, discusses recent advances in our understanding of lesional macrophage phenotype and function in different stages of atherosclerosis. With the increasing understanding of the roles of lesional macrophages, new research areas and treatment strategies are beginning to emerge.