申请者报道并提出磷酸肌醇激酶3（PI3K）信号通路介导apelin-13促进单核细胞-血管内皮细胞粘附参与APJ受体及其配体apelin促进动脉粥样硬化发展新观点，预实验发现apelin-13诱导血管内皮细胞自噬、促进NADPH oxidase 4(NOX4)表达和活性氧（ROS）生成，据此提出NOX4-自噬途径介导apelin促单核细胞-血管内皮细胞粘附的假说。课题拟明确apelin诱导血管内皮细胞自噬、自噬介导apelin促进单核细胞-血管内皮细胞粘附的影响；用RNA干扰等技术探讨NOX4-自噬途径是否介导apelin促单核细胞-血管内皮细胞粘附；分析体内高表达或沉默apelin对apoE-/-小鼠动脉粥样硬化斑块和自噬影响。阐明自噬参与apelin促单核细胞-血管内皮细胞粘附的新机理，为动脉粥样硬化防治提供实验依据。

We reported for the first time that apelin-13 enhance monocyte-endothelial cells adhesion mediated by phosphoinositide 3 kinase (PI3K) signaling transduction pathway and G-protein coupled receptor APJ and endogenous ligand apelin system are reported to promote atherosclerosis,but it's molecular mechanism unclearly.Recently we find that apelin-13 induce autophagy、increases expression of NADPH oxdase 4(NOX4) and reactive oxygen species(ROS)in endothelial cells in pre-experiments.Hypothesis is that NOX4-autophagy pathway may involve in monocyte-endothelial cells adhesion induced by apelin.We will investigate that apelin effects on autophagy、monocyte-endothelial cell adhesion,chemotaxis in vitro;we will study that NOX4-autophagy pathway mediate monocyte-endothelial cell adhesion stimulated by apelin in siRNA and others;We will test that apelin effect on atherosclerosis and autophagy in apoE-/-atherosclerosis mice model by using high and low apelin expression technology.This hypothesis will show new mechenism that apelin/APJ system participate in progression of atherosclerosis in details.