线粒体自噬-Warburg效应介导apelin促血管平滑肌细胞增殖

项目名称： 线粒体自噬-Warburg效应介导apelin促血管平滑肌细胞增殖

项目编号： No.81470434

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 陈临溪

作者单位： 南华大学

项目金额： 68万元

中文摘要： 申请者首先报道NADPH氧化酶4（NOX4）源性活性氧（ROS）介导APJ受体内源性配体apelin-13促血管平滑肌细胞（VSMC）增殖；预实验发现apelin-13 上调VSMC的AMPKα磷酸化、诱导线粒体自噬、促进有氧条件下乳酸生成（有氧糖酵解反应即Warburg效应），据此提出线粒体自噬-Warburg效应介导apelin促血管平滑肌细胞增殖科学假说。课题拟采用RNA干扰等方法，探讨apelin-13是否诱导VSMC线粒体自噬；明确apelin-13是否诱导VSMC Warburg效应；分析线粒体自噬是否调节apelin-13诱导的VSMC Warburg效应；揭示线粒体自噬-Warburg效应是否介导apelin-13促VSMC增殖。课题从线粒体自噬-Warburg效应新视角阐明apelin/APJ系统促VSMC增殖新机制，为揭示动脉硬化等血管增生性疾病发病机理提供依据。

中文关键词： 氧化应激；线粒体；血管平滑肌细胞；动脉粥样硬化

英文摘要： Applicant first reported NADPH oxidase 4 (NOX4)-derived reactive oxygen species (ROS) mediated APJ receptor endogenous ligand apelin-13 stimulate vascular smooth muscle cells (VSMC) proliferation; Preliminary experiments found that apelin-13 increases VSMC AMPKα phosphorylation, induces mitophagy， promote lactate production under aerobic conditions(aerobic glycolysis reaction that Warburg effect), pursuant to that mitophagy-Warburg effect pathway mediated vascular smooth muscle cell proliferation induced by apelin scientific hypothesis. Topics to be adopted RNA interference, to explore whether apelin-13-induced VSMC mitophagy; Clear whether apelin-13 induced VSMC Warburg effect; analyze whether mitophagy regulate apelin-induced VSMC Warburg effect; Reveal mitophagy-Warburg effect mediated apelin-13 induced VSMC proliferation. From mitophagy-Warburg effect new perspective ,to clarify apelin / APJ system to promote VSMC proliferation of new mechanisms.To provide a basis for revealing the pathogenesis of atherosclerosis and other vascular disorders.

英文关键词： oxidative stress;mitochondria;vascular smooth muscle cell;atherosclerosis