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.

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). 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. 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. D-4F effectively protects vascular endothelial cells against ox-LDL-induced injury by preventing the downregulation of PEDF expression.