Vascular Smooth Muscle Cells in Atherosclerosis.
Vascular Smooth Muscle Cells in Atherosclerosis.
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DOI：
10.1161/circresaha.115.306361
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发表时间：
2016-02-19
影响因子：
20.1
通讯作者：
Owens GK
中科院分区：
文献类型：
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作者：
Bennett MR;Sinha S;Owens GK
血管平滑肌细胞(VSMCs)在动脉粥样硬化中的历史观点是，VSMCs的异常增殖促进斑块的形成，但进展期斑块中的VSMCs完全是有益的，例如防止纤维帽的破裂。然而，这一观点是基于斑块内存在同质的VSMCs群体的想法，可以使用标准的VSMC和巨噬细胞免疫组织化学‘标记物’将其与其他斑块细胞(特别是巨噬细胞)分开识别。最近的遗传谱系追踪研究表明，VSMC表型转换导致分化较少的形式，缺乏包括巨噬细胞样细胞在内的VSMC‘标记’，这种转换直接促进动脉粥样硬化。此外，VSMC的增殖在整个动脉粥样硬化过程中可能是有益的，而不仅仅是在晚期病变中，而VSMC的凋亡、细胞衰老和VSMC来源的巨噬细胞样细胞可能促进炎症。我们综述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，VSMCs不同来源的证据，以及VSMCs在动脉粥样硬化中所经历的个别过程在斑块形成和晚期病变结构中的作用。我们认为，现在有令人信服的证据表明，充分了解血管平滑肌细胞在动脉粥样硬化中的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。
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 believe there is now compelling evidence that a full understanding of VSMC behavior in atherosclerosis is critical to identifying therapeutic targets to both prevent and treat atherosclerosis.