Effect of oxidized low-density lipoprotein on survival and function of endothelial progenitor cell mediated by p38 signal pathway.
This study was designed to investigate whether oxidized low-density lipoprotein (oxLDL) affects the survival and activity of endothelial progenitor cell (EPC) mediated by p38 mitogen-activated protein kinase (MAPK). EPCs were isolated from human peripheral blood in endothelial cell growth medium-2. Incubation with oxLDL at 100 microg/mL decreased EPC number. Treated with oxLDL resulted in increase of EPC apoptosis and in decrease of EPC proliferation. Treatment with oxLDL resulted in a significantly reduced migratory rate of EPCs and reduced adhesion to fibronectin. Treatment with oxLDL impaired the in vitro angiogenesis ability of EPCs. However, all the detrimental effects on EPC were attenuated by pretreatment of EPCs with SB203580, an inhibitor of the p38 MAPK. In addition, the inhibition of the p38-kinase by SB203580 also significantly improved basal number and functions of EPCs. Western blot analysis revealed that oxLDL induced dose- and time-dependent activation of the p38 MAPK. These results demonstrated that p38 MAPK plays a critical role in regulating the number and functions of EPCs in vitro. SB203580 can improve the number and functions of EPCs under basal conditions and prevent the negative effects of oxLDL on the number and functions of EPCs and may be useful to improve the number and function of EPCs for potential cell therapy.
Wu
Yonggang
Y
National Center of Human Stem Cell Research and Engineering, Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha, Hunan, China.
Wang
Qiru
Q
Cheng
Lamei
L
Wang
Jian
J
Lu
Guangxiu
G
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology* / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
D007093:Imidazoles; D008077:Lipoproteins, LDL; D011725:Pyridines; C099252:oxidized low density lipoprotein; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580