Ox-LDL induces endothelial cell apoptosis and macrophage migration by regulating caveolin-1 phosphorylation
Ox-LDL induces endothelial cell apoptosis and macrophage migration by regulating caveolin-1 phosphorylation
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Ox-LDL通过调节caveolin-1磷酸化诱导内皮细胞凋亡和巨噬细胞迁移
DOI：
10.1002/jcp.26468
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发表时间：
2018-10-01
影响因子：
5.6
通讯作者：
Li, Min
中科院分区：
文献类型：
--
作者：
Lin, Fei;Pei, Likai;Li, Min
氧化低密度脂蛋白（ox-LDL）是动脉粥样硬化的危险因素。氧化低密度脂蛋白在动脉粥样硬化的初始阶段导致内皮损伤。在这项研究中，我们研究了ox-LDL在内皮损伤和巨噬细胞募集中的作用。我们证明，ox-LDL促进剂量依赖性的人脐静脉内皮细胞中的小窝蛋白-1的磷酸化。磷酸化小窝蛋白-1增加ox-LDL摄取。ox-LDL在细胞内的蓄积可诱导NF-Bp 65磷酸化，促进HMGB 1从细胞核向细胞质的转位和细胞色素C从线粒体向细胞质的释放，并激活caspase 3，导致细胞凋亡。NF-B活化也促进cavolin-1磷酸化和HMGB 1表达。此外，小窝蛋白-1磷酸化有利于HMGB 1的释放和EGR 1的核转位。EGFR 1的核转位促进了HMGB 1的胞质转位。细胞外HMGB 1以TLR 4依赖的方式诱导PMBC源性巨噬细胞向HUVECs迁移。提示ox-LDL通过调节caveolin-1的磷酸化水平促进HUVECs凋亡和巨噬细胞的募集。
Oxidative low-density lipoprotein (ox-LDL) is a risk factor for atherosclerosis. Ox-LDL leads to endothelial injury in the initial stage of atherosclerosis. In this study, we investigated the role of ox-LDL in endothelial injury and macrophage recruitment. We demonstrated that ox-LDL promoted a dose-dependent phosphorylation of caveolin-1 in human umbilical vein endothelial cells. Phosphorylated caveolin-1 increased ox-LDL uptake. Intracellular accumulation of ox-LDL induced NF-B p65 phosphorylation, promoted HMGB1 translocation from nucleus to cytoplasm and cytochrome C release from mitochondria to cytoplasm, and activated caspase 3, resulting in cell apoptosis. NF-B activation also facilitated cavolin-1 phosphorylation and HMGB1 expression. In addition, caveolin-1 phosphorylation favored HMGB1 release and nuclear translocation of EGR1. Nuclear translocation of EGR1 contributed to cytoplasmic translocation of HMGB1. The extracellular HMGB1 induced the migration of PMBC-derived macrophages toward HUVECs in a TLR4-dependent manner. Our results suggested that ox-LDL promoted HUVECs apoptosis and macrophage recruitment by regulating caveolin-1 phosphorylation.