[Gly14]-Humanin Prevents Lipid Deposition and Endothelial Cell Apoptosis in a Lectin-like Oxidized Low-density Lipoprotein Receptor-1-Dependent Manner
[Gly14]-Humanin Prevents Lipid Deposition and Endothelial Cell Apoptosis in a Lectin-like Oxidized Low-density Lipoprotein Receptor-1-Dependent Manner
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[Gly14]-Humanin 以凝集素样氧化低密度脂蛋白受体 1 依赖性方式防止脂质沉积和内皮细胞凋亡
DOI：
10.1002/lipd.12195
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发表时间：
2019-10-01
期刊：
影响因子：
1.9
通讯作者：
Liu, Huihui
中科院分区：
文献类型：
--
作者：
Ding, Yu;Feng, Yue;Liu, Huihui
氧化型低密度脂蛋白（Ox-LDL）可诱导血管内皮细胞凋亡和功能障碍，参与动脉粥样硬化的发生和发展，而凝集素样氧化型低密度脂蛋白受体1（LOX-1）在动脉粥样硬化形成过程中对Ox-LDL的摄取起重要作用。Humanin（HN）是一种脑源性肽，最近被证明对内皮功能障碍和Ox-LDL诱导的动脉粥样硬化进展发挥保护作用。HN类似物HNGF 6A（HNG）调节巨噬细胞RAW 264.7细胞中的胆固醇代谢。然而，HNG是否影响内皮细胞中的Ox-LDL代谢尚不清楚。本研究探讨了HNG对人脐静脉内皮细胞（HUVEC）氧化低密度脂蛋白（Ox-LDL）蓄积的影响及其机制。HUVEC与HNG预孵育1 h，然后加入Ox-LDL。通过使用组织总胆固醇测定试剂盒和流式细胞术测量总胆固醇含量。通过CCK 8测定法测量细胞活力。蛋白质含量通过蛋白质印迹分析来检查。流式细胞仪检测凋亡细胞。流式细胞术和组织总胆固醇测定表明，HNG减少ox-LDL在HUVEC中的积累。HNG还能抑制Ox-LDL诱导的HUVEC凋亡。Western blot结果显示HNG降低LOX-1蛋白含量。然而，当LOX-1被敲低或抑制时，HNG减少Ox-LDL聚集和凋亡的作用消失。我们的研究表明HNG以LOX-1依赖的方式减少HUVEC中的脂质聚集和凋亡。
Oxidized low-density lipoprotein (Ox-LDL) may induce apoptosis and dysfunction of vascular endothelial cells, contributing to the initiation and development of atherosclerosis and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) plays a central role in Ox-LDL uptake in the course of atherogenesis. Humanin (HN), a mitochondrial-derived peptide, was recently demonstrated to exert a protective role against endothelial dysfunction and Ox-LDL-induced progression of atherosclerosis. The HN analog HNGF6A (HNG) modulates cholesterol metabolism in macrophage RAW 264.7 cells. However, whether HNG affects Ox-LDL metabolism in endothelial cells is unknown. In this study, we investigated the effect of HNG on Ox-LDL accumulation in human umbilical vein endothelial cell (HUVEC) and its underlying mechanisms. HUVEC were preincubated with HNG for 1 h before addition of Ox-LDL. Total cholesterol content was measured by using a tissue total cholesterol assay kit and flow cytometry. Cell viability was measured by CCK8 assay. Protein content was examined by Western blot assays. Flow cytometry was used to identify apoptotic cells. Flow cytometry and tissue total cholesterol assays showed that HNG reduced Ox-LDL accumulation in HUVEC. In addition, HNG inhibited Ox-LDL-induced apoptosis of HUVEC. Western blot results showed that HNG reduced LOX-1 protein content. However, when LOX-1 was knocked down or inhibited, the effect of HNG in reducing Ox-LDL aggregation and apoptosis in HUVEC disappeared. Our study demonstrated that HNG reduces lipid aggregation and apoptosis in HUVEC in a LOX-1-dependent manner.