PP2A调控动脉粥样硬化中泡沫细胞形成的机制研究

泡沫细胞形成是动脉粥样硬化的重要病理基础，多种磷酸化信号通路参与其调控。我们前期研究发现人动脉粥样硬化组织中，PP2A酶——一种在细胞内广泛存在的蛋白磷酸酶，其表达与正常对照相比具有显著差异。而在细胞实验中通过抑制PP2A活性可以减少泡沫细胞形成。结合文献，我们推测PP2A可能对动脉粥样硬化形成中泡沫细胞的功能具有重要调节作用。因此设计本研究：拟首先检测人动脉粥样硬化组织内PP2A表达及活性变化；进一步通过体外细胞实验，使用磷酸蛋白组学分析PP2A调控泡沫细胞形成的信号通路，并通过小分子药物抑制剂或基因沉默技术确认信号通路，以阐明PP2A对泡沫细胞形成的具体调节机制；最后通过基因敲除与药物阻断的方式验证抑制PP2A是否具有减缓小鼠动脉粥样硬化发生的效果。通过本研究，有望揭示PP2A调控动脉粥样硬化中泡沫细胞形成的机制，为治疗动脉粥样硬化提供新靶点。

Foam cell formation is an important artery pathological characteristic of atherosclerosis. Multiple phosphorylation signaling pathways involved in the regulation of foam cell formation. Our preliminary study found that compared with controls expression of PP2A enzymes –a protein phosphatases existing extensive in cells, was significantly different in human atherosclerotic tissue. In cell experiments foam cell formation was reduced by inhibiting PP2A activity. Combined with literature, we hypothesized that PP2A may play an important role in foam cell formation during atherosclerosis. Therefore, we design the study: Firstly，measure PP2A expression and activity in human atherosclerotic tissue; Secondly in vitro experiments, we plan to analysis phosphatase proteomics to find out signaling pathways change regulated by PP2A in foam cell formation, as well by small molecule inhibitors or gene silencing techniques confirm the signal pathway and clarify the exact regulatory mechanisms of PP2A in foam cell formation; Finally by gene knockout or molecular inhibitor blocking the pathway to verify whether inhibiting PP2A has the effect of slowing atherosclerosis in vivo. Through this study, it is expected to reveal the PP2A regulatory mechanisms of foam cells formation in atherosclerosis, providing new targets for treatment of atherosclerosis.