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Ox‐LDL induces endothelial cell apoptosis and macrophage migration by regulating caveolin‐1 phosphorylation
Author(s) -
Lin Fei,
Pei Likai,
Zhang Qingbin,
Han Weizhong,
Jiang Shiliang,
Lin Yanliang,
Dong Bo,
Cui Lianqun,
Li Min
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26468
Subject(s) - phosphorylation , microbiology and biotechnology , apoptosis , cytoplasm , hmgb1 , umbilical vein , foam cell , oxidative phosphorylation , macrophage , chemistry , biology , biochemistry , receptor , in vitro
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.