Submitted on November 21, 2005
Revised on February 14, 2006
Accepted on March 6, 2006
Oxidized low density lipoprotein impairs endothelial progenitor cells by regulation of endothelial nitric oxide synthase
Feng Xia Ma, Bin Zhou, Zhong Chen, Qian Ren, Shi Hong Lu, Tatsuya Sawamura, and Zhong Chao Han
Institute of Hematology, Chinese Academy of Medical Sciences & Peking Union of Medical College, Tianjin 30020
Corresponding Author: tihzchan{at}public.tpt.tj.cn
Oxidized low density lipoprotein (oxLDL) serves as 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 EPCs survival and impaired its adhesive, migratory and tube formation capacities in a dose-dependent fashion. However, all the detrimental effects of oxLDL were attenuated by pretreatment of EPCs with LOX-1 monoclonal antibody (LOX-1 mAb) 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 EPCs survival and impaires its function, and this action is due to an inhibitory effect on eNOS.