出版社：American Society for Biochemistry and Molecular Biology
摘要：Oxidized low density lipoprotein (OxLDL) is one of the mostimportant risk factors of cardiovascular disease. Here, we studythe impact of OxLDL on endothelial progenitor cells (EPCs) anddetermine whether OxLDL affects EPCs by an inhibitory effecton endothelial nitric oxide synthase (eNOS). It was found thatOxLDL decreased EPC survival and impaired its adhesive, migratory,and tube-formation capacities in a dose-dependent manner. However,all of the detrimental effects of OxLDL were attenuated by pretreatmentof EPCs with lectin-like oxidized low density lipoprotein receptor(LOX-1) monoclonal antibody or L-arginine. Western blot analysisrevealed that OxLDL dose-dependently decreased Akt phosphorylationand eNOS protein expression and increased LOX-1 protein expression.Furthermore, OxLDL caused a decrease in eNOS mRNA expressionand an increase in LOX-1 mRNA expression. These data indicatethat OxLDL inhibits EPC survival and impairs its function, andthis action is attributable to an inhibitory effect on eNOS.Supplementary key words angiogenesis • stem cell • apoptosis • Akt
Abbreviations: Dil Ac-LDL, 1,1'-dioctadecyl-3,3,3'3' -tetramethylindocar-bocyanine perchlorate (Dil)-labeled acetylated low density lipoprotein; eNOS, endothelial nitric oxide synthase; EPC, endothelial progenitor cell; HUVEC, human umbilical vein endothelial cell; L-NAME, N-nitro-L-arginine methyl ester; LOX-1, lectin-like oxidized low density lipoprotein receptor; LOX-1 MAb, lectin-like oxidized low density lipoprotein receptor monoclonal antibody; MNC, mononuclear cell; NO, nitric oxide; OxLDL, oxidized low density lipoprotein; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling; UEA-1, Ulex europaeus agglutinin-1; VEGF, vascular endothelial growth factor
