ROS-Autophagy pathway mediates monocytes-human umbilical vein endothelial cells adhesion induced by apelin-13
ROS-Autophagy pathway mediates monocytes-human umbilical vein endothelial cells adhesion induced by apelin-13
复制标题
ROS-自噬通路介导apelin-13诱导的单核细胞-人脐静脉内皮细胞粘附
DOI：
10.1002/jcp.26554
复制
发表时间：
2018-10-01
影响因子：
5.6
通讯作者：
Chen, Linxi
中科院分区：
文献类型：
--
作者：
Liu, Meiqing;Li, Hening;Chen, Linxi
Apelin是APJ受体的内源性配体。单核细胞（MC）和人脐静脉内皮细胞（HUVECs）均表达apelin和APJ，它们在动脉粥样硬化的生理过程中起重要作用。我们前期的研究表明apelin-13促进MCs-HUVECs粘附。在此，我们进一步探讨负责由apelin-13诱导的MCs-HUVECs粘附的机制。Apelin-13促进HUVECs中活性氧（ROS）的产生和NOX 4的表达。Apelin-13诱导HUVECs自噬，增加beclin 1和LC 3-II/I蛋白表达，诱导自噬流，NAC、过氧化氢酶和DPI可阻断Apelin-13诱导的自噬流。NAC和过氧化氢酶抑制apelin-13诱导的自噬通量，但不抑制羟氯喹（HCQ）。NAC、过氧化氢酶和DPI阻止爱帕琳-13诱导的HUVEC中ICAM-1表达。雷帕霉素增强MCs-HUVECs粘附，NAC、过氧化氢酶和DPI可逆转该粘附。通过siRNA下调beclin 1和LC 3的表达可阻断MCs-HUVECs的粘附。Apelin-13诱导ApoE-/-（HFD）小鼠模型中动脉粥样硬化斑块并增加N 0X 4、LC 3-II/I表达。我们的研究结果表明，apelin-13通过ROS-自噬途径诱导MCs-HUVECs粘附。
Apelin is the endogenous ligand of APJ receptor. Both monocytes (MCs) and human umbilical vein endothelial cells (HUVECs) express apelin and APJ, which play important roles in the physiological processes of atherosclerosis. Our previous research indicated that apelin-13 promoted MCs-HUVECs adhesion. Here, we further explore the mechanism responsible for MCs-HUVECs adhesion induced by apelin-13. Apelin-13 promoted reactive oxygen species (ROS) generation and NOX4 expression in HUVECs. Apelin-13 inducedautophagy, increased proteins beclin1 and LC3-II/I expression and induced autophagy flux in HUVECs, which was blocked by NAC, catalase and DPI. Autophagy flux induced by apelin-13 was inhibited by NAC and catalase but not hydroxychloroquine (HCQ). NAC, catalase, and DPI prevented apelin-13 induced ICAM-1 expression in HUVECs. Rapamycin enhanced MCs-HUVECs adhesion that was reversed by NAC, catalase, and DPI. Down-regulation of beclin1 and LC3 by siRNA blocked MCs-HUVECs adhesion. Apelin-13 induced atherosclerotic plaque and increased NOX4, LC3-II/I expression in ApoE-/-(HFD) mouse model. Our results demonstrated that apelin-13 induced MCs-HUVECs adhesion via a ROS-autophagy pathway.