[Gly14]-Humanin Prevents Lipid Deposition and Endothelial Cell Apoptosis in a Lectin-like Oxidized Low-density Lipoprotein Receptor-1-Dependent Manner

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.

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