Oxidized low density lipoprotein impairs endothelial progenitor cells by regulation of endothelial nitric oxide synthase |
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Authors: | Ma Feng Xia Zhou Bin Chen Zhong Ren Qian Lu Shi Hong Sawamura Tatsuya Han Zhong Chao |
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Affiliation: | State Key Laboratory of Experimental Hematology and National Research Center for Stem Cell Engineering and Technology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China. |
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Abstract: | 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. |
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Keywords: | angiogenesis stem cell apoptosis Akt |
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