CD137信号调节内皮-间质细胞转化在动脉粥样硬化血管新生中的作用及机制研究

动脉粥样硬化（AS）易损斑块破裂的主要致病机制为斑块内内皮-间质细胞转化（End-MT），其中转化生长因子 β（TGF-β）信号对斑块内End-MT起着重要作用。我们前期研究发现：小鼠动脉粥样硬化病变严重部位CD137和P-Smad2/3表达显著增加，内皮细胞表面内皮细胞特异性蛋白下调，间充质特异性蛋白上调；CD137对内皮细胞有促进增殖、迁移作用；抑制CD137信号能明显抑制斑块发展。因此，我们提出如下假说：CD137通过调控TGF-β-Smad信号介导AS 斑块内发生End-MT。本研究在前期基础上，分别以ApoE-/-小鼠及内皮细胞为模型，观察CD137对TGF-β-Smad信号及End-MT的影响，明确CD137如何调控TGF-β-Smad信号致End-MT,阐明易损斑块内End-MT现象的机制，为易损斑块破裂的防治带来新契机。

Endothelial-to-Mesenchymal Transition（End-MT）is a key mechanism of atherosclerotic plaques rupture，in which Transforming growth factor β（TGF-β）signaling plays an important role. In our previous studies, we show that the expression of CD137 and P-Smad2/3 increased significantly in advanced atherosclerotic plaques of mice, endothelial cell specific protein down-regulated, and mesenchymal specific protein up-regulated. Activation of CD137 signaling induces activation of Smad, endothelial proliferation, migration and tube formation. Blocking CD137 signaling could inhibit this activation and attenuated CD137 antibody-induced atherosclerosis formation and development. These dates raise the possibility that CD137/ TGF-β-smad signaling interaction promotes End-MT in atherosclerosis.On the basis of the preliminary work, ApoE-/- mice, Human umbilical vein endothelial cells, mouse brain microvascular endothelial cells are used to investigate whether CD137 signaling acts as a modulating of TGF-β pathway on End-MT in atherosclerosis. We would illustrate that the mechanism of CD137/TGF-β-Smad signaling interaction in regulating the progression of End-MT in advanced AS plaque.This provides a new opportunity for the prevention and treatment of vulnerable plaque rupture.