Vascular smooth muscle cell phenotypic plasticity: focus on chromatin remodelling.
Vascular smooth muscle cell phenotypic plasticity: focus on chromatin remodelling.
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DOI：
10.1093/cvr/cvs098
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发表时间：
2012-07
影响因子：
10.8
通讯作者：
J. Spin;L. Maegdefessel;P. Tsao
中科院分区：
文献类型：
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作者：
J. Spin;L. Maegdefessel;P. Tsao
分化的血管平滑肌细胞（SMC）保留了响应炎症或损伤而改变其表型的能力。这种表型转换是血管疾病的重要组成部分，并且部分依赖于表观遗传调节。在文献中已经建立了一个评价，染色质重塑在SMC谱系确定和影响SMC行为和状态变化中起着重要作用。该过程包括许多染色质调控元件和途径，例如组蛋白乙酰转移酶、脱乙酰酶和甲基转移酶以及作用于SMC特异性标记位点以沉默或允许进入细胞转录机器的其他因子，以及作用于其他关键调控元件例如心肌蛋白和Kruppel样因子4（KLF 4）的其他因子。已知改变SMC表型的各种刺激物，如转化生长因子β（TGF-β）、血小板衍生生长因子（PDGF）、氧化磷脂和视黄酸，似乎部分通过影响SMC染色质结构发挥作用。近年来，已经确定了建立SMC确定性的特定共价组蛋白修饰，而其他修饰则改变了分化状态。在这篇文章中，我们回顾了染色质重塑的机制，因为它适用于SMC表型。
Differentiated vascular smooth muscle cells (SMCs) retain the capacity to modify their phenotype in response to inflammation or injury. This phenotypic switching is a crucial component of vascular disease, and is partly dependent on epigenetic regulation. An appreciation has been building in the literature for the essential role chromatin remodelling plays both in SMC lineage determination and in influencing changes in SMC behaviour and state. This process includes numerous chromatin regulatory elements and pathways such as histone acetyltransferases, deacetylases, and methyltransferases and other factors that act at SMC-specific marker sites to silence or permit access to the cellular transcriptional machinery and on other key regulatory elements such as myocardin and Kruppel-like factor 4 (KLF4). Various stimuli known to alter the SMC phenotype, such as transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF), oxidized phospholipids, and retinoic acid, appear to act in part through effects upon SMC chromatin structure. In recent years, specific covalent histone modifications that appear to establish SMC determinacy have been identified, while others alter the differentiation state. In this article, we review the mechanisms of chromatin remodelling as it applies to the SMC phenotype.