Mechanisms that regulate macrophage burden in atherosclerosis.
Mechanisms that regulate macrophage burden in atherosclerosis.
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DOI：
10.1161/circresaha.114.301174
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发表时间：
2014-05-23
影响因子：
20.1
通讯作者：
Randolph GJ
中科院分区：
文献类型：
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作者：
Randolph GJ
与动脉粥样硬化相关的单核巨噬细胞(MPS)包括单核细胞、巨噬细胞和树突状细胞(DC)。十年前，对动脉粥样硬化病变中巨噬细胞行为的研究往往局限于对斑块横截面中巨噬细胞总面积的量化。虽然仍然需要技术进步来以日益动态和信息丰富的方式检查斑块MP种群，但最近几年发展起来的询问动脉粥样硬化斑块中MPS生物学的创新方法指出了许多调节MPS在斑块内积累和功能的机制。在这里，我回顾了动脉粥样硬化斑块从斑块的起始到进展和消退的演变过程，讨论了在这些不同的疾病阶段，MPS的募集、增殖和保留所起的作用。未来还需要进行更多的工作，以更好地区分斑块中的巨噬细胞和DC，并解决该领域的一些基本未知问题，包括胆固醇是如何促使巨噬细胞在病变中积累以建立斑块的，以及巨噬细胞作为先天免疫的主要效应者如何与适应性免疫反应的组成部分一起推动动脉粥样硬化。寻求这些问题的答案的目的是在存在疾病的地方逆转疾病，在没有疾病的地方防止疾病的发展。
Mononuclear phagocytes (MPs) relevant to atherosclerosis include monocytes, macrophages, and dendritic cells (DCs). A decade ago, studies on macrophage behavior in atherosclerotic lesions were often limited to quantification of total macrophage area in cross-sections of plaques. While technological advances are still needed to examine plaque MP populations in an increasingly dynamic and informative manner, innovative methods to interrogate the biology of MPs in atherosclerotic plaques developed in the last few years point to a number of mechanisms that regulate the accumulation and function of MPs within plaques. Here, I review the evolution of atherosclerotic plaques with respect to changes in the MP compartment from the initiation of plaque to its progression and regression, discussing the roles that recruitment, proliferation, and retention of MPs play at these different disease stages. Additional work in the future will be needed to better distinguish macrophages and DCs in plaque and to address some basic unknowns in the field, including just how cholesterol drives accumulation of macrophages in lesions to build plaques in the first place and how macrophages as major effectors of innate immunity work together with components of the adaptive immune response to drive atherosclerosis. Answers to these questions are sought with the goal in mind of reversing disease where it exists and preventing its development where it does not.