Department of Cardiology, Shandong Energy Zibo Mining Group Co., Ltd Central Hospital, Zibo, China.
Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
J Cell Physiol. 2018 Oct;233(10):6683-6692. doi: 10.1002/jcp.26468. Epub 2018 May 9.
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-κB 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-κB 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.
氧化型低密度脂蛋白（ox-LDL）是动脉粥样硬化的危险因素。ox-LDL 导致动脉粥样硬化的初始阶段内皮损伤。在这项研究中，我们研究了 ox-LDL 在血管内皮损伤和巨噬细胞募集中的作用。我们证明 ox-LDL 可促进人脐静脉内皮细胞 caveolin-1 的剂量依赖性磷酸化。磷酸化的 caveolin-1 增加 ox-LDL 的摄取。ox-LDL 的细胞内积累诱导 NF-κB p65 的磷酸化，促进 HMGB1 从核到细胞质的易位和细胞色素 C 从线粒体到细胞质的释放，并激活 caspase 3，导致细胞凋亡。NF-κB 的激活也促进了 cavolin-1 的磷酸化和 HMGB1 的表达。此外，caveolin-1 的磷酸化有利于 HMGB1 的释放和 EGR1 的核易位。核易位的 EGR1 有助于细胞质中 HMGB1 的易位。细胞外 HMGB1 以 TLR4 依赖的方式诱导 PMBC 衍生的巨噬细胞向 HUVEC 迁移。我们的结果表明，ox-LDL 通过调节 caveolin-1 的磷酸化促进 HUVECs 凋亡和巨噬细胞募集。
