Institute for Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.
Queen's Medical Research Institute, University of Edinburgh, 47 Little Crescent, Edinburgh EH16 4TJ, UK.
Cell Signal. 2019 Jan;53:90-101. doi: 10.1016/j.cellsig.2018.09.004. Epub 2018 Sep 15.
Excessive vascular smooth muscle cell (SMC) proliferation, migration and extracellular matrix (ECM) synthesis are key events in the development of intimal hyperplasia, a pathophysiological response to acute or chronic sources of vascular damage that can lead to occlusive narrowing of the vessel lumen. Atherosclerosis, the primary cause of coronary artery disease, is characterised by chronic vascular inflammation and dyslipidemia, while revascularisation surgeries such as coronary stenting and bypass grafting represent acute forms of vascular injury. Gene knockouts of transforming growth factor-beta (TGFβ), its receptors and downstream signalling proteins have demonstrated the importance of this pleiotropic cytokine during vasculogenesis and in the maintenance of vascular homeostasis. Dysregulated TGFβ signalling is a hallmark of many vascular diseases, and has been associated with the induction of pathological vascular cell phenotypes, fibrosis and ECM remodelling. Here we present an overview of TGFβ signalling in SMCs, highlighting the ways in which this multifaceted cytokine regulates SMC behaviour and phenotype in cardiovascular diseases driven by intimal hyperplasia.
血管平滑肌细胞（SMC）的过度增殖、迁移和细胞外基质（ECM）的合成是内膜增生的关键事件，内膜增生是对血管损伤的急性或慢性来源的一种病理生理反应，可导致血管腔的闭塞性狭窄。动脉粥样硬化是冠心病的主要原因，其特征为慢性血管炎症和血脂异常，而血管成形术如冠状动脉支架置入术和旁路移植术则代表了急性血管损伤的形式。转化生长因子-β（TGFβ）、其受体和下游信号蛋白的基因敲除已经证明了这种多功能细胞因子在血管生成和维持血管内稳态中的重要性。TGFβ信号的失调是许多血管疾病的一个标志，并与诱导病理性血管细胞表型、纤维化和 ECM 重塑有关。在这里，我们概述了 TGFβ信号在 SMC 中的作用，强调了这种多方面的细胞因子如何调节由内膜增生驱动的心血管疾病中 SMC 的行为和表型。
