Atherosclerosis is a chronic inflammatory disease that progresses to complex, unstable arterial lesions.1 Restenosis is an acute inflammatory vascular disease and a major limitation of percutaneous angioplasty procedures.2 Both are characterized by dedifferentiation of vascular smooth muscle cells (SMCs) resulting in neointimal hyperplasia and vessel occlusion. Differentiated SMCs are highly specialized cells whose primary role is to maintain vessel homeostasis, vessel tone, blood pressure, and blood flow distribution.3 This function is driven through expression of SMC-specific contractile and contractile-related proteins, including SMMHC (smooth muscle myosin heavy chain/ Myh11 ), α-SMA (α-smooth muscle actin/ Acta2 ), SM22α ( Tagln1 ), and calponin ( Cnn1 ), among others. Unlike terminally differentiated cardiac and skeletal muscle, SMCs retain a significant degree of phenotypic plasticity, exhibiting the ability to undergo extensive changes in phenotype in response to specific stimuli (ie, dedifferentiated SMC). SMC dedifferentiation is associated with a transition to a highly proliferative, inflammatory phenotype characterized by downregulation of SMC-specific genes and increased production of multiple inflammatory and matrix-associated mediators. Thus, SMCs are major contributors to vascular disease progression, and defining molecular mechanisms regulating SMC phenotypic transitions is critical to define novel therapeutics for the treatment of vascular disease. Article, see p 628 Regulation of SMC differentiation is complex, involving multiple signaling pathways and transcriptional regulators. Most SMC-specific genes are under transcriptional control by the transcription factor, serum response factor (SRF), and its cardiac and SMC-specific cofactor, myocardin, the SRF–myocardin axis.3–5 SRF binds the serum response element or CArG box, in which one or more are present within promoter and intronic regions of SMC-specific genes.3,4 In contrast, myocardin does not directly bind DNA, but transactivates SMC-specific genes through its interaction with SRF.5 Although the SRF–myocardin axis is central to transcriptional regulation of SMC genes, additional factors and mechanisms have been …

中文翻译：

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平滑的肌肉分化控制来了整整一圈

动脉粥样硬化是一种慢性炎性疾病，会发展成复杂，不稳定的动脉病变。1再狭窄是一种急性炎性血管疾病，是经皮血管成形术的主要局限性。2两者均以血管平滑肌细胞（SMC）脱分化为特征，导致新内膜增生和血管闭塞。分化的SMC是高度专业化的细胞，其主要作用是维持血管稳态，血管张力，血压和血流分布。3此功能是通过表达SMC特异性收缩蛋白和收缩相关蛋白（包括SMMHC（平滑肌肌球蛋白））来驱动的。重链/ Myh11），α-SMA（α-平滑肌肌动蛋白/ Acta2），SM22α（Tagln1）和钙蛋白（Cnn1）等。与终末分化的心肌和骨骼肌不同，SMC保留了很大程度的表型可塑性，表现出响应特定刺激（即去分化的SMC）而在表型上发生广泛变化的能力。SMC去分化与向高度增殖的炎症表型的转变有关，其特征在于SMC特异性基因的下调以及多种炎症和基质相关介体的产生增加。因此，SMC是血管疾病进展的主要贡献者，并且定义调节SMC表型转变的分子机制对于定义用于治疗血管疾病的新疗法至关重要。文章，请参见第628页。SMC分化的调控是复杂的，涉及多个信号传导途径和转录调控因子。