title: Silent information regulator 1 (SIRT1) promotes the migration and proliferation of endothelial progenitor cells through the PI3K/Akt/eNOS signaling pathway.
abstract: Silent information regulator 1 (SIRT1) mediates many effects of caloric restriction (CR) on an organism's lifespan and metabolic pathways. Recent reports have also emphasized its role in vascular function. The present study was designed to investigate the effects of SIRT1 on the properties of mouse spleen derived endothelial progenitor cells (EPCs). SIRT1 in EPCs was significantly increased by serum and by vascular endothelial growth factor (VEGF). Moreover, an adenovirus (Ad) vector expressing SIRT1 (Ad-SIRT1)-mediated overexpression of SIRT1 directly enhanced migration and proliferation of EPCs, whereas silencing of endogenous SIRT1 in EPCs inhibited cell functions. In addition, LY294002 (a PI3K inhibitor), sc-221226 (an Akt inhibitor), and L-NAME (an NOS inhibitor) abolished Ad-SIRT1-induced migration and proliferation of EPCs, and prevented nitric oxide (NO) production. Phosphorylation of Akt, PI3K, and endothelial nitricoxide synthase (eNOS) were up-regulated by Ad-SIRT1, which was attenuated by LY294002, sc-221226, and L-NAME. Together, the results suggested that through the PI3K/Akt/eNOS signaling pathway, SIRT1 plays an important role in the biological properties of EPCs.
authors.affiliation: Department of Cardiology, 305 Hospital of PLA Beijing 100017, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Cardiology, 305 Hospital of PLA Beijing 100017, China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Du
authors.affiliation: Cadre Ward Two, Wuhan General Hospital of Guangzhou Military Command Wuhan 430070, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiology, 305 Hospital of PLA Beijing 100017, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, 305 Hospital of PLA Beijing 100017, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Lai
authors.affiliation: Department of Cardiology, 305 Hospital of PLA Beijing 100017, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Department of Cardiology, 305 Hospital of PLA Beijing 100017, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Cardiology, 305 Hospital of PLA Beijing 100017, China.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, 305 Hospital of PLA Beijing 100017, China.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Zong
authors.affiliation: Department of Cardiology, 305 Hospital of PLA Beijing 100017, China.
authors.forename: Yuntian
authors.initials: Y
authors.lastname: Li
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D066026:Endothelial Progenitor Cells / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation; D005822:Genetic Vectors; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: Silent information regulator 1; endothelial progenitor cells; migration; proliferation