title: Short time tripterine treatment enhances endothelial progenitor cell function via heat shock protein 32.
abstract: The dysfunction of endothelial progenitor cells (EPCs) limits their potential for the treatment of ischemia and atherosclerosis. Therefore, we investigated the effect of tripterine on EPC function and examined the underlying mechanisms. The effect of tripterine, an active component of Tripterygium wilfordii Hook, on the enhancement of EPC function and the efficiency of EPC transplantation was investigated in vitro and in vivo. Treatment of EPCs with tripterine at 2.5 µM for 4 h inhibited oxidized low-density lipoprotein (ox-LDL) induced ROS production, cell apoptosis, and cell senescence and improved the migration and tube formation capacities of EPCs treated with ox-LDL (200 µg/ml). In vivo studies showed that tripterine conditioning of EPCs administered to ischemic foci improved blood perfusion and microvascular density in a mouse hindlimb ischemia model. Examination of the underlying mechanisms indicated that the effect of tripterine is mediated by the induction of heat shock protein 32 expression and the inhibition of JNK activation. The present results are of clinical significance because they suggest the potential of tripterine as a therapeutic agent to improve the efficacy of EPC transplantation for the treatment of ischemic diseases.
authors.affiliation: Department of Interventional Radiology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China; Shanghai Gong Li Hospital, Shanghai, China.
authors.forename: Chenhui
authors.initials: C
authors.lastname: Lu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.forename: Denghai
authors.initials: D
authors.lastname: Zhang
authors.forename: Erli
authors.initials: E
authors.lastname: Pei
authors.forename: Jichong
authors.initials: J
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Tang
authors.forename: Meng
authors.initials: M
authors.lastname: Ye
authors.forename: Georges
authors.initials: G
authors.lastname: Uzan
authors.forename: Kangkang
authors.initials: K
authors.lastname: Zhi
authors.forename: Maoquan
authors.initials: M
authors.lastname: Li
authors.forename: Keqiang
authors.initials: K
authors.lastname: Zuo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002469:Cell Separation; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D066026:Endothelial Progenitor Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D053978:Pentacyclic Triterpenes; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C099252:oxidized low density lipoprotein; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases; C050414:celastrol