title: The mTOR/AP-1/VEGF signaling pathway regulates vascular endothelial cell growth.
abstract: Vascular restenosis is a common adverse event following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). The atypical Ser/Thr protein kinase mammalian target of rapamycin (mTOR) plays an important role in cell differentiation and apoptosis. Vascular restenosis caused by excessive endothelial cell proliferation can be inhibited by local application of the mTOR inhibitor rapamycin (RAPA); however, RAPA can also suppress normal vascular endothelial cell growth by blocking mTOR/VEGF signaling, although the underlying mechanism is still unclear. Here, endogenous mTOR, AP-1, and VEGF were inhibited or overexpressed to investigate the mechanism underlying the effects of RAPA. Inhibition of AP-1 or mTOR with AP-1-siRNA or RAPA treatment respectively, decreased vascular endothelial cell proliferation, upregulation of AP-1 or mTOR increased cell proliferation, and VEGF overexpression increased, while RAPA-induced mTOR inhibition decreased vascular endothelial cell proliferation, the results indicate that combining mTOR downregulation and VEGF upregulation might both inhibit restenosis and maintain normal vascular endothelial cell growth after PCI or CABG, suggest the mTOR/AP-1/VEGF pathway might play a crucial role in regulating vascular endothelial cell growth.
authors.affiliation: Medical College, Nantong University, Nantong, China.|Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Wang
authors.affiliation: Medical College, Nantong University, Nantong, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: You
authors.affiliation: Department of Pathology, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Immunology, Nantong University, Nantong, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D034622:RNA Interference; D051381:Rats; D015398:Signal Transduction / Q000235:genetics*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D018808:Transcription Factor AP-1; D042461:Vascular Endothelial Growth Factor A; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: AP-1; VEGF; mTOR; signaling pathway; vascular endothelial cell