心肌素抑制血管平滑肌细胞表型转换改善动脉粥样硬化

Myocardin inhibits the phenotype switch of vascular smooth muscle cell to improve atherosclerosis

动脉粥样硬化(As)是一种涉及多种细胞并由多种因素诱导的慢性疾病,血管平滑肌细胞(VSMC)的增殖、迁移对As的发生和发展有着不可忽视的影响,包括促进斑块的生成及诱发斑块的不稳定等。VSMC由收缩表型向合成表型转换是其增殖和迁移的基础,维持VSMC的收缩表型,抑制其合成表型的形成有助于抑制其异常增殖和As斑块的形成。心肌素作为VSMC收缩标志基因的关键转录因子,能与血清反应因子结合来激活VSMC收缩标志基因的表达。多种功能因子,如雌激素受体α、组蛋白修饰、DNA甲基化和microRNA等,都可以与心肌素联合作用调节血管的功能并抑制VSMC的表型转换;多种作用途径,例如转化生长因子β1、血小板衍生生长因子BB等信号通路,可增加心肌素表达,抑制VSMC的增殖和迁移。因此,心肌素在As发展过程中有着至关重要的保护作用。调控心肌素影响VSMC的表型转换可能成为未来治疗As乃至心血管疾病的新策略。

Atherosclerosis （As） is a chronic disease involving several kinds of cells and induced by a variety of factors. The proliferation and migration of vascular smooth muscle cell （VSMC） have an important influence on the occurrence and development of As, including the promotion of the plaque formation and the instability of the plaque. Conversion of VSMC from contractile phenotype to synthetic phenotype is the basis of VSMC proliferation and migration. The maintanance of VSMC contractile phenotype is helpful to inhibit its abnormal proliferation and the plaque formation. Myocardin, as the key transcription factors of VSMC contraction marker genes, binds to serum response factor to facilitate expression of VSMC contraction marker genes. Many kinds of functional factors such as estrogen receptor or, histone modification, DNA methylation and microRNA, can be combined with myocardin, regulating vascular function and inhibiting the phenotype switch of VSMC; various channels, such as transforming growth factor-β1 and platelet derived growth factor-BB signaling pathway, can increase expression of myocardin to inhibit the proliferation and migration of VSMC. So myocardin plays an important role in the development of As. Regulating myocardin to affect the phenotype switch of VSMC may become a new therapeutic strategy for As and other cardiovascular diseases in the future.