title: Glycogen synthase kinase 3β inhibition enhanced proliferation, migration and functional re-endothelialization of endothelial progenitor cells in hypercholesterolemia microenvironment.
abstract: Hypercholesterolemia impairs the quantity and function of endothelial progenitor cell. We hypothesized that glycogen synthase kinase 3β activity is involved in regulating biological function of endothelial progenitor cells in hypercholesterolemia microenvironment. For study, endothelial progenitor cells derived from apolipoprotein E-deficient mice fed with high-fat diet were used. Glycogen synthase kinase 3β activity was interfered with glycogen synthase kinase 3β inhibitor lithium chloride or transduced with replication defective adenovirus vector expressing catalytically inactive glycogen synthase kinase 3β (GSK3β-KM). Functions of endothelial progenitor cells, proliferation, migration, secretion and network formation of endothelial progenitor cells were assessed in vitro. The expression of phospho-glycogen synthase kinase 3β, β-catenin and cyclinD1 in endothelial progenitor cells was detected by Western blot. The in vivo function re-endothelialization and vasodilation were also analyzed by artery injury model transplanted with glycogen synthase kinase 3β-inhibited endothelial progenitor cells. We demonstrated that while the proliferation, migration, network formation as well as VEGF and NO secretion were impaired in apolipoprotein E-deficient endothelial progenitor cells, glycogen synthase kinase 3β inhibition significantly improved all these functions. Apolipoprotein E-deficient endothelial progenitor cells showed decreased phospho-glycogen synthase kinase 3β, β-catenin and cyclinD1 expression, whereas these signals were enhanced by glycogen synthase kinase 3β inhibition and accompanied with β-catenin nuclear translocation. Our in vivo model showed that glycogen synthase kinase 3β inhibition remarkably increased re-endothelial and vasodilation. Taken together, our data suggest that inhibition of glycogen synthase kinase 3β is associated with endothelial progenitor cell biological functions both in vitro and in vivo. It might be an important interference target in hypercholesterolemia microenvironment.
authors.affiliation: Institute of Cardiovascular disease of PLA, Xinqiao Hospital, Third military Medical University, Chongqing 400037, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Cui
authors.affiliation: Institute of Cardiovascular disease of PLA, Xinqiao Hospital, Third military Medical University, Chongqing 400037, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Jin
authors.affiliation: Institute of Cardiovascular disease of PLA, Xinqiao Hospital, Third military Medical University, Chongqing 400037, People's Republic of China.
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Ding
authors.affiliation: Institute of Cardiovascular disease of PLA, Xinqiao Hospital, Third military Medical University, Chongqing 400037, People's Republic of China.
authors.forename: Mengyang
authors.initials: M
authors.lastname: Deng
authors.affiliation: Institute of Cardiovascular disease of PLA, Xinqiao Hospital, Third military Medical University, Chongqing 400037, People's Republic of China.
authors.forename: Shiyong
authors.initials: S
authors.lastname: Yu
authors.affiliation: Institute of Cardiovascular disease of PLA, Xinqiao Hospital, Third military Medical University, Chongqing 400037, People's Republic of China.
authors.forename: MingBao
authors.initials: M
authors.lastname: Song
authors.affiliation: Institute of Cardiovascular disease of PLA, Xinqiao Hospital, Third military Medical University, Chongqing 400037, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Institute of Cardiovascular disease of PLA, Xinqiao Hospital, Third military Medical University, Chongqing 400037, People's Republic of China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Institute of Cardiovascular disease of PLA, Xinqiao Hospital, Third military Medical University, Chongqing 400037, People's Republic of China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of Cardiovascular disease of PLA, Xinqiao Hospital, Third military Medical University, Chongqing 400037, People's Republic of China huanglan260@126.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D066026:Endothelial Progenitor Cells / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D006937:Hypercholesterolemia / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3
keywords: Endothelial progenitor cell; endothelium; glycogen synthase kinase; hypercholesterolemia; lithium