TBX20通过调控血管周围脂肪干细胞分化抑制糖尿病血管内膜新生的分子机制研究

动脉粥样硬化性心脑血管疾病（ASCVD）为糖尿病致死致残最重要的原因。内膜新生在糖尿病ASCVD发生发展过程中扮演了重要角色。高血糖及胰岛素抵抗加速了内膜新生的发生。我们前期研究证实血管周围存在脂肪干细胞，scRNA-seq提示血管周围脂肪干细胞（PV-ADSC）高表达TBX20。既往研究显示TBX20与心脏发育、血管重构有关，且高糖直接影响TBX20表达。预实验发现TBX20影响PV-ADSC血管系分化。提示TBX20可能是PV-ADSC参与糖尿病血管病变的关键作用因子及潜在治疗靶点。本研究拟在前期研究基础上通过体外细胞实验和动物实验的方法阐明TBX20调控PV-ADSC血管系分化和抑制内膜新生的机制，筛选鉴定其关键作用蛋白以明确分子机制并鉴定其信号通路。为糖尿病内膜新生靶向治疗提供理论依据。

Atherosclerotic cardiovascular disease (ASCVD) contributes to major cause of mortality and morbidity in diabetes mellitus. Neointimal hyperplasia (NIH) plays an important role in ASCVD. Hyperglycemia and insulin resistance accelerates NIH. Our previous study identified adipose-derived stem cells (ADSCs) from perivascular adipose tissue and showed that the expression of TBX20 in perivascular ADSCs (PV-ADSCs) was high by scRNA-seq. TBX20 played an important role in heart development and vascular remodeling, as well as PV-ADSCs differentiation. Additionally, TBX20 activity was regulated by glucose lever. These observations indicated that TBX20 might serve as potential target for PV-ADSCs intervention in diabetic vasculopathy. Based on our previous study, we will investigate the mechanism in the inhibition of NIH by TBX20 and PV-ADSCs differentiation. Furthermore, we will identify the key TBX20-interacting proteins and their binding structure by tandem affinity purification to explore the underlining molecular mechanism, as well as the signaling pathway, which will provide targeted therapy of NIH in diabetic patients.