title: VEGF increases the proliferative capacity and eNOS/NO levels of endothelial progenitor cells through the calcineurin/NFAT signalling pathway.
abstract: We have investigated whether VEGF (vascular endothelial growth factor) regulates the proliferative capacity and eNOS (endothelial nitric oxide synthase)/NO (nitric oxide) pathway of EPCs (endothelial progenitor cells) by activating CaN (calcineurin)/NFAT (nuclear factor of activated T-cells) signalling. EPCs were obtained from cultured mononuclear cells isolated from the peripheral blood of healthy adults. Treatment with VEGF (50 ng/ml) potently promoted CaN enzymatic activity, activation of NFAT2, cell proliferation, eNOS protein expression and NO production. Pretreatment with cyclosporin A (10 μg/ml), a pharmacological inhibitor of CaN or 11R-VIVIT, a special inhibitor of NFAT, completely abrogated the aforementioned effects of VEGF treatment and increased apoptosis. The results indicate that VEGF treatment promotes the proliferative capacity of human EPCs by activating CaN/NFAT signalling leading to increased eNOS protein expression and NO production.
authors: Zunyi Hospital, The Third Affiliated Hospital of Zunyi Medical College, Guizhou Province, Zunyi City 563002, People’s Republic of China. yanglong1002@hotmail.com
authors: Long
authors: L
authors: Yang
authors: Hongshan
authors: H
authors: Guan
authors: Jionghong
authors: J
authors: He
authors: Liqun
authors: L
authors: Zeng
authors: Zhengqiang
authors: Z
authors: Yuan
authors: Min
authors: M
authors: Xu
authors: Wenhui
authors: W
authors: Zhang
authors: Xiaole
authors: X
authors: Wu
authors: Jing
authors: J
authors: Guan
mesh_terms: D017209:Apoptosis; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D050778:NFATC Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D016572:Cyclosporine; D052250:Nitric Oxide Synthase Type III; D019703:Calcineurin