CD137信号介导VSMC衰老及免疫清除障碍促进血管老化机制研究

血管老化是老年血管疾病的发病基础，衰老血管平滑肌细胞（VSMC）的增多和免疫清除障碍是其中的关键因素。我们前期研究发现CD137在老年小鼠血管VSMC中表达增高。体外实验显示，小鼠原代培养的同代VSMC，敲除CD137后衰老细胞比例较野生型明显减少。共培养实验发现衰老VSMC能抑制T细胞对其清除，而CD137-/-VSMC无此功能。因此，我们提出如下假说：CD137信号介导VSMC衰老与免疫清除障碍促进血管老化。本项目在前期基础上探讨：（1）CD137信号对血管老化及老年血管功能的影响。（2）CD137信号诱导VSMC衰老以及衰老相关因子（SASP）分泌的机制（通过何种信号分子，SASP种类、成分）。（3）CD137信号介导衰老VSMC免疫清除障碍的机制（调控T细胞功能）。本研究将有望为延缓血管老化提供新的思路。

Vascular aging is the basis of the pathogenesis of senile vascular diseases. The increase of senescent vascular smooth muscle cells (VSMCs) and impaired immune clearance are the key factors. Our previous research found that CD137 expression was increased in vascular VSMCs in aged mice. In vitro experiments showed that the proportion of senescent cells in the primary cultured VSMCs of mice was significantly reduced compared to the wild type after CD137 was knocked out. Co-cultivation experiments found that senescent VSMCs can inhibit T cells from eliminating them, but CD137-/-VSMCs do not have this function. Therefore, we propose the following hypothesis: CD137 signaling mediates VSMC aging and immune clearance disorders promote blood vessel aging. This project explores on a preliminary basis: (1) the effect of CD137 signal on vascular aging and senile vascular function. (2) The mechanism of CD137 signal-induced VSMC aging and the secretion of senescence-related factors (SASP) (by which signal molecule, SASP type and composition). (3) The mechanism of CD137 signal-mediated immune clearance disorder in aging VSMCs (regulating T cell function). This study is expected to provide new ideas for delaying vascular aging.