血管平滑肌细胞（VSMC）增殖是动脉粥样硬化（AS）的关键环节。IIA型分泌型磷脂酶A2（sPLA2-IIA）与心血管疾病关系密切，但其在AS过程中对VSMC增殖的调节及其机制尚未不明确。我们前期发现心血管疾病患者血清中sPLA2-IIA水平增高；过表达sPLA2-IIA可促进离体VSMC增殖，MCP-1等多个增殖相关基因表达改变，AKT通路激活，抑制AKT通路逆转上述作用。故推测sPLA2-IIA可能通过AKT通路调节VSMC增殖参与AS发病。本课题组拟借助离体细胞模型研究：1)sPLA2-IIA对VSMC增殖功能的促进作用和对相关基因表达谱的影响；2)该作用所依赖的信号通路，主要为AKT。考察sPLA2-IIA调节VSMC增殖、促进AS发病的机制，可为AS的防治提供理论和实验依据。

The proliferation of vascular smooth muscle cells (VSMC) is a key part in atherosclerosis. Secretory phospholipase A2 group IIA (sPLA2-IIA) is closely associated with cardiovascular disease. However, in the progression of atherosclerosis, its regulatory effects on VSMC proliferation and the involved mechanisms are still unclear. We previously found that the serum level of sPLA2-IIA was increased in patients with cardiovascular disease, while overexpression of sPLA2-IIA could promote VSMC proliferation in vitro, paralleled with changes in the expression of proliferation-related genes including MCP-1, and activation of AKT pathway, whereas inhibition of AKT showed reversed effects. Hence we speculate that sPLA2-IIA might regulate VSMC proliferation through AKT pathway and thus play a role in the progression of atherosclerosis. The present project plans to investigate the followings by using in vitro cell culture model: 1) promoting effect of sPLA2-IIA on VSMC proliferative function and on the expression profile of related genes; 2) the signaling pathway on which such effect depends, with emphasis on AKT. Investigating the mechanism of sPLA2-IIA on modulating VSMC proliferation and promoting the pathogenesis of atherosclerosis, could provide theoretic and experimental basis for prevention and treatment of atherosclerosis.

IIA型分泌型磷脂酶A2（sPLA2-IIA）与心血管疾病关系密切，但其在动脉粥样硬化过程中对血管平滑肌细胞（VSMC）增殖的调节及其机制尚未不明确。本项目借助体外细胞培养模型，建立稳定过表达sPLA2-IIA的大鼠胸主动脉平滑肌细胞株，观察到OxLDL存在条件下sPLA2-IIA对VSMC增殖具有促进作用。我们进一步以qPCR array技术对sPLA2-IIA所调控的VSMC增殖相关基因进行全面的考察和筛选。通过运用AKT信号通路抑制剂，我们初步发现sPLA2-IIA调控VSMC增殖可能该通路激活有关。上述研究结果有助于理解sPLA2-IIA对VSMC增殖的影响和对VSMC增殖相关基因的调控作用，可为进一步研究sPLA2-IIA在动脉粥样硬化发生发展过程中的作用和机制提供理论依据。