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血管平滑肌细胞的激活:蛋白质组学观点。

Vascular smooth-muscle-cell activation: proteomics point of view.

机构信息

Institute of Clinical Physiology-CNR, Pisa, Italy.

出版信息

Int Rev Cell Mol Biol. 2011;288:43-99. doi: 10.1016/B978-0-12-386041-5.00002-9.

DOI:10.1016/B978-0-12-386041-5.00002-9
PMID:21482410
Abstract

Vascular smooth-muscle cells (VSMCs) are the main component of the artery medial layer. Thanks to their great plasticity, when stimulated by external inputs, VSMCs react by changing morphology and functions and activating new signaling pathways while switching others off. In this way, they are able to increase the cell proliferation, migration, and synthetic capacity significantly in response to vascular injury assuming a more dedifferentiated state. In different states of differentiation, VSMCs are characterized by various repertories of activated pathways and differentially expressed proteins. In this context, great interest is addressed to proteomics technology, in particular to differential proteomics. In recent years, many authors have investigated proteomics in order to identify the molecular factors putatively involved in VSMC phenotypic modulation, focusing on metabolic networks linking the differentially expressed proteins. Some of the identified proteins may be markers of pathology and become useful tools of diagnosis. These proteins could also represent appropriately validated targets and be useful either for prevention, if related to early events of atherosclerosis, or for treatment, if specific of the acute, mid, and late phases of the pathology. RNA-dependent gene silencing, obtained against the putative targets with high selective and specific molecular tools, might be able to reverse a pathological drift and be suitable candidates for innovative therapeutic approaches.

摘要

血管平滑肌细胞(VSMCs)是动脉中层的主要组成部分。由于其巨大的可塑性,当受到外部刺激时,VSMCs 通过改变形态和功能,并激活新的信号通路,同时关闭其他信号通路来做出反应。通过这种方式,它们能够在血管损伤时显著增加细胞增殖、迁移和合成能力,从而呈现出更去分化的状态。在不同的分化状态下,VSMCs 的特征是激活途径和差异表达蛋白的不同组合。在这种情况下,人们对蛋白质组学技术,特别是差异蛋白质组学产生了极大的兴趣。近年来,许多作者研究了蛋白质组学,以鉴定可能参与 VSMC 表型调节的分子因素,重点是代谢网络中连接差异表达蛋白的分子。一些已鉴定的蛋白可能是病理学的标志物,并成为诊断的有用工具。这些蛋白还可以代表经过适当验证的靶点,无论是针对动脉粥样硬化早期事件的预防,还是针对病理学的急性、中期和晚期的治疗都非常有用。针对潜在靶点使用高选择性和特异性的分子工具进行 RNA 依赖性基因沉默,可能能够逆转病理性漂移,成为创新治疗方法的候选者。

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