Vascular Biology and Translational Research, Department of Pathology, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia.
Cardiovascular Research Institute, University of California, San Francisco, CA, United States of America.
Vascul Pharmacol. 2022 Oct;146:107091. doi: 10.1016/j.vph.2022.107091. Epub 2022 Jul 25.
Vascular smooth muscle cells (SMC) possess a unique cytoplasticity, regulated by transcriptional, translational and phenotypic transformation in response to a diverse range of extrinsic and intrinsic pathogenic factors. The mature, differentiated SMC phenotype is physiologically typified transcriptionally by expression of genes encoding "contractile" proteins, such as SMα-actin (ACTA2), SM-MHC (myosin-11) and SM22α (transgelin). When exposed to various pathological conditions (e.g., pro-atherogenic risk factors, hypertension), SMC undergo phenotypic modulation, a bioprocess enabling SMC to de-differentiate in immature stages or trans-differentiate into other cell phenotypes. As recent studies suggest, the process of SMC phenotypic transformation involves five distinct states characterized by different patterns of cell growth, differentiation, migration, matrix protein expression and declined contractility. These changes are mediated via the action of several transcriptional regulators, including myocardin and serum response factor. Conversely, other factors, including Kruppel-like factor 4 and nuclear factor-κB, can inhibit SMC differentiation and growth arrest, while factors such as yin yang-1, can promote SMC differentiation whilst inhibiting proliferation. This article reviews recent advances in our understanding of regulatory mechanisms governing SMC phenotypic modulation. We propose the concept that transcription factors mediating this switching are important biomarkers and potential pharmacological targets for therapeutic intervention in cardiovascular disease.
血管平滑肌细胞 (SMC) 具有独特的细胞质可塑性，这种可塑性通过转录、翻译和表型转化来调节，以响应各种外在和内在的致病因素。成熟的、分化的 SMC 表型在生理上表现为编码“收缩”蛋白的基因表达，如 SMα-肌动蛋白 (ACTA2)、SM-MHC（肌球蛋白-11）和 SM22α（转胶蛋白）。当暴露于各种病理条件（例如，动脉粥样硬化风险因素、高血压）时，SMC 会经历表型调节，这是一个使 SMC 去分化为未成熟阶段或转分化为其他细胞表型的生物过程。正如最近的研究表明，SMC 表型转化的过程涉及五个不同的状态，其特征是不同的细胞生长、分化、迁移、基质蛋白表达和收缩性下降模式。这些变化是通过几种转录调节剂的作用介导的，包括心肌营养素和血清反应因子。相反，其他因素，如 Kruppel 样因子 4 和核因子-κB，可以抑制 SMC 分化和生长停滞，而 Yin Yang-1 等因素可以促进 SMC 分化，同时抑制增殖。本文综述了我们对调节 SMC 表型调节的机制的理解的最新进展。我们提出了这样的概念，即介导这种转换的转录因子是心血管疾病治疗干预的重要生物标志物和潜在的药理学靶点。
