D-4F, an Apolipoprotein A-I Mimetic Peptide, Protects Human Umbilical Vein Endothelial Cells From Oxidized Low-Density Lipoprotein–induced Injury by Preventing the Downregulation of Pigment Epithelium-derived Factor Expression

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Abstract
Aim: To investigate the protective effects of D-4F, an apolipoprotein A-I mimetic peptide, on oxidized low-density lipoprotein (ox-LDL)–induced injury of vascular endothelial cells and the potential role of pigment epithelium–derived factor (PEDF). Methods: Cytotoxicity was assessed by the apoptotic rate, 3-(4,5-dimethylthiazol-2-y-l)-2,5-diphenyl-2H-tetrazolium bromide assay, and lactate dehydrogenase release. PEDF levels were analyzed with Western blot and quantitative real-time polymerase chain reaction. Redox status was measured by the levels of the reactive oxygen species, malondialdehyde, superoxide dismutase, and nitric oxide. Results: Ox-LDL reduced cell viability and induced apoptosis and LDH release from human umbilical vein endothelial cells, but the cytotoxic effects of ox-LDL were significantly inhibited by pretreatment with D-4F. Additionally, D-4F could scavenge intracellular reactive oxygen species, suppress the production of lipid peroxides, and improve endogenous antioxidant activity. Ox-LDL decreased PEDF expression in human umbilical vein endothelial cells in a concentration-dependent manner, and this decrease was markedly attenuated by D-4F. However, silencing PEDF by short interfering RNA blocked the inhibitory effects of D-4F on ox-LDL–induced oxidative stress and cellular injury. Conclusions: D-4F effectively protects vascular endothelial cells against ox-LDL–induced injury by preventing the downregulation of PEDF expression.

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