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Vascular Smooth Muscle Cells in Atherosclerosis

机译:动脉粥样硬化中的血管平滑肌细胞

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The historical view of vascular smooth muscle cells (VSMCs) in atherosclerosis is that aberrant proliferation of VSMCs promotes plaque formation, but that VSMCs in advanced plaques are entirely beneficial, for example preventing rupture of the fibrous cap. However, this view has been based on ideas that there is a homogenous population of VSMCs within the plaque, that can be identified separate from other plaque cells (particularly macrophages) using standard VSMC and macrophage immunohistochemical markers. More recent genetic lineage tracing studies have shown that VSMC phenotypic switching results in less-differentiated forms that lack VSMC markers including macrophage-like cells, and this switching directly promotes atherosclerosis. In addition, VSMC proliferation may be beneficial throughout atherogenesis, and not just in advanced lesions, whereas VSMC apoptosis, cell senescence, and VSMC-derived macrophage-like cells may promote inflammation. We review the effect of embryological origin on VSMC behavior in atherosclerosis, the role, regulation and consequences of phenotypic switching, the evidence for different origins of VSMCs, and the role of individual processes that VSMCs undergo in atherosclerosis in regard to plaque formation and the structure of advanced lesions. We think there is now compelling evidence that a full understanding of VSMC behavior in atherosclerosis is critical to identify therapeutic targets to both prevent and treat atherosclerosis.
机译:动脉粥样硬化中血管平滑肌细胞(VSMC)的历史观点是,VSMC的异常增殖会促进斑块的形成,而晚期斑块中的VSMC则完全有益,例如,防止纤维帽破裂。但是,这种观点是基于这样的想法,即斑块内存在同质的VSMC,可以使用标准VSMC和巨噬细胞免疫组织化学标记物与其他斑块细胞(尤其是巨噬细胞)分开识别。最近的遗传谱系追踪研究表明,VSMC表型转换导致分化程度较低的形式缺乏包括巨噬细胞样细胞在内的VSMC标记,并且这种转换直接促进了动脉粥样硬化。此外,VSMC增殖可能在整个动脉粥样硬化中有益,而不仅仅是在晚期病变中,而VSMC凋亡,细胞衰老和VSMC衍生的巨噬细胞样细胞可能促进炎症。我们回顾了胚胎起源对动脉粥样硬化中VSMC行为的影响,表型转换的作用,调节和后果,VSMC不同起源的证据以及VSMC在斑块形成和结构方面在动脉粥样硬化中所经历的各个过程的作用。晚期病变。我们认为,现在有令人信服的证据表明,充分了解动脉粥样硬化中VSMC行为对于确定预防和治疗动脉粥样硬化的治疗靶点至关重要。

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