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Journal of Lipid Research, Vol. 47, 1227-1237, June 2006 Oxidized low density lipoprotein impairs endothelial progenitor cells by regulation of endothelial nitric oxide synthase
* State Key Laboratory of Experimental Hematology and National Research Center for Stem Cell Engineering and Technology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China Published, JLR Papers in Press, March 7, 2006.
1 To whom correspondence should be addressed. e-mail: tihzchan{at}public.tpt.tj.cn Oxidized low density lipoprotein (OxLDL) is one of the most important risk factors of cardiovascular disease. Here, we study the impact of OxLDL on endothelial progenitor cells (EPCs) and determine whether OxLDL affects EPCs by an inhibitory effect on endothelial nitric oxide synthase (eNOS). It was found that OxLDL 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 pretreatment of EPCs with lectin-like oxidized low density lipoprotein receptor (LOX-1) monoclonal antibody or L-arginine. Western blot analysis revealed that OxLDL dose-dependently decreased Akt phosphorylation and eNOS protein expression and increased LOX-1 protein expression. Furthermore, OxLDL caused a decrease in eNOS mRNA expression and an increase in LOX-1 mRNA expression. These data indicate that OxLDL inhibits EPC survival and impairs its function, and this 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
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