支架内再狭窄是血运重建后不良预后的独立预测因子之一。新生内膜形成是再狭窄的重要病理特征，而血管损伤后平滑肌细胞（SMCs）增殖能力增强、合成大量细胞外基质是形成新生内膜的关键环节。细胞骨架蛋白Testin可以调节细胞的迁移及信号转导等重要生理过程，但Testin与新生内膜形成的关系及其对SMCs功能的调控目前尚无报道。我们的前期研究发现：血管损伤致新生内膜形成处Testin表达降低，损伤局部过表达Testin可以抑制新生内膜形成。此外，PDGF可以下调SMCs中Testin表达水平，而过表达Testin可以抑制SMCs增殖。据此推测，Testin通过抑制病理性促增殖因子介导的SMCs增殖，进而影响新生内膜形成。本研究拟建立小鼠新生内膜形成模型及损伤血管局部过表达/敲除Testin小鼠进行整体研究，同时使用原代SMCs培养等手段进行机制研究，以阐明Testin在新生内膜形成过程中的作用。

The in-stent restenosis as an independent predictor of adverse cardiac events, often leads to poor prognosis of patients after percutaneous coronary intervention. Neointimal hyperplasia is an important pathological feature of vascular restenosis, and refers to post-intervention, pathological, vascular remodeling due to proliferation and migration of vascular smooth muscle cells (SMCs) in the tunica intima layer. SMCs in neointimal hyperplasia lose contractile phenotype, and they differentiate into secretory phenotype predominantly. These modified SMCs secrete the growth factors, extracellular matrix and inflammatory mediators responsible to neointimal hyperplasia. Testin is a cytoskeletal protein that mediates cell migration and participates in associated signaling pathways. However, thus far, the role and mechanism of Testin in neointimal hyperplasia and SMC proliferation is still unclear. Our preliminary data suggested that: in a left common carotid arterial wire injury model, increased neointimal hyperplasia was observed with decreased Testin expression, while injured arteries of lentiviral Testin overexpression-treated rat showed a significant reduced in the intima/media ratio. It is well known that platelet-derived growth factor (PDGF) is increased in the neointima and is a strong promoter for SMC proliferation. We tested the effect of PDGF stimulation in human aorta SMCs on Testin expression and found that PDGF also decreased Testin expression. And lentiviral Testin overexpression inhibited PDGF-induced cell proliferation in human aorta SMCs. These data indicate that Testin blocks neointimal hyperplasia through regulation of pathological growth factors-mediated SMC proliferation. Thus, in the current study, we will establish mouse neointimal formation models and lentiviral Testin overexpression/knockdown in the mouse injured arteries, and use cultured primary SMCs to explore the potential role and underlying mechanisms of Testin in neointimal hyperplasia. Targeting Testin activity may have potential in the treatment of vessel narrowing diseases.