title: Hepatocyte growth factor protects endothelial progenitor cell from damage of low-density lipoprotein cholesterol via the PI3K/Akt signaling pathway.
abstract: Risk factors for coronary heart disease including low-density lipoprotein (LDL) cholesterol can reduce the number and activity of endothelial progenitor cells (EPCs), thereby hindering their usefulness for treating cardiovascular disease in transplants. The aim of this study was to investigate whether hepatocyte growth factor (HGF) can protect EPCs from the inhibition caused by LDL cholesterol. EPCs derived from mouse bone marrow were isolated and cultured in medium supplemented with different concentrations of LDL cholesterol. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, modified Boyden chambers and flow cytometry were used to evaluate EPC proliferation, migration and apoptosis. The role of Akt in this process was also evaluated through observing the expressions of total Akt and Akt phosphorylation, and pharmacological analysis. Our results indicate that LDL cholesterol inhibits the proliferation and migration of EPCs, and induces their apoptosis. However, HGF improves the activity of EPCs inhibited by LDL cholesterol, and it simultaneously decreases EPC apoptosis induced by LDL cholesterol. Blockade of phosphoinositide-3 kinase (PI3K) by Ly294002 attenuates the effect of HGF. Furthermore, our experiments suggest that HGF increases the level of phosphorylated Akt in EPCs rather than Akt. However, PI3K inhibitor reduces the increase of phosphorylated Akt level induced by HGF. These findings suggest HGF promotes endothelial progenitor cells migration, proliferation and survival impaired by low-density lipoprotein cholesterol via the PI3K/Akt signaling pathway.
authors.affiliation: Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, 400037 Chongqing, People's Republic of China.
authors.forename: XueJun
authors.initials: X
authors.lastname: Yu
authors.forename: MingBao
authors.initials: M
authors.lastname: Song
authors.forename: JianFei
authors.initials: J
authors.lastname: Chen
authors.forename: GuangXu
authors.initials: G
authors.lastname: Zhu
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Lan
authors.initials: L
authors.lastname: Hunag
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D008078:Cholesterol, LDL / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects*; D042783:Endothelial Cells / Q000166:cytology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology
chemical_list: D008078:Cholesterol, LDL; D017228:Hepatocyte Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D019859:Proto-Oncogene Proteins c-met; D051057:Proto-Oncogene Proteins c-akt
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