vinexin β在血管损伤后新生内膜增生中的作用及其机制

Vinexinβ是参与调节细胞粘附，细胞骨架组合以及生长因子信号转导的衔接蛋白。目前国内外关于vinexinβ对血管内膜新生的作用及其机理的研究尚无相关报道。本项目拟从动物，细胞和分子水平系统阐明vinexinβ在新生内膜增生中的作用及其机制。第一部分，运用vinenexinβ基因敲除和血管平滑肌特异性转基因小鼠建立颈动脉导丝损伤模型，研究vinexinβ对血管新生内膜增生的影响。第二部分，分离培养vinexin β基因敲除和血管平滑肌特异性转基因小鼠和野生型小鼠血管平滑肌细胞，研究vinexin β对血管平滑肌细胞增殖和迁移的影响。第三部分，在大鼠血管平滑肌细胞中通过RNA干扰和过表达载体抑制或上调vinexinβ的表达，探讨vinexinβ作用的可能的分子机制。力图明确vinexinβ在内膜新生中的作用及其对平滑肌细胞增殖、迁移作用的根本机制，为内膜新生相关疾病的防治提供新的分子靶点。

Vinexin β, a novel ubiquitously expressed adaptor protein, has been implicated in cell adhesion, cytoskeleton organization and growth factor signal transduction. However, the role of vinexin β in neointima formation remains unclear. The proposed research consists of three parts to clarify the role and mechanism of vinexin β in neointima formation at cell, animal and molecular levels. In the first part, the vinexinβknockout and vascular smooth muscle specific transgenic mice will be used to study the effect of vinexin β on neointima hyperplasia after carotid wire injury. In the second part, to clarify the role of vinexin β in proliferation and migration of vascular smooth muscle cell, the primary vascular smooth muscle cell from vinexin β knockout and vascular smooth muscle specific transgenic mice will be isolated and treated with platelet derived growth factor(PDGF-BB). In the third part, Advinexin β and Adshvinexin β adenoviruses will be used to infect primary rat vascular smooth muscle cell to get overexpression or downregulation of vinexin β, and the molecular mechanism of vinexin β will be investigated. We try to clarify the role and mechanism of vinexin β in neointima formation and provide new molecular target for prevention and therapy of neointima formation.