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VEGF increases the proliferative capacity and eNOS/NO levels of endothelial progenitor cells through the calcineurin/NFAT signalling pathway

Authors

  • Long Yang,

    Corresponding author
    1. Zunyi Hospital, The Third Affiliated Hospital of Zunyi Medical College, Guizhou Province, Zunyi City 563002, Peoples Republic of China
    2. Guizhou Provincial Cardiovascular Institute, Guizhou Province, Guiyang City 550002, Peoples Republic of China
      These authors contributed equally to the study. To whom correspondence should be addressed (email yanglong1002@hotmail.com).
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  • Hongshan Guan,

    Corresponding author
    1. Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100037, Peoples Republic of China
      These authors contributed equally to the study.
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  • Jionghong He,

    1. Zunyi Hospital, The Third Affiliated Hospital of Zunyi Medical College, Guizhou Province, Zunyi City 563002, Peoples Republic of China
    2. Guizhou Provincial Cardiovascular Institute, Guizhou Province, Guiyang City 550002, Peoples Republic of China
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  • Liqun Zeng,

    1. Zunyi Hospital, The Third Affiliated Hospital of Zunyi Medical College, Guizhou Province, Zunyi City 563002, Peoples Republic of China
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  • Zhengqiang Yuan,

    1. Zunyi Hospital, The Third Affiliated Hospital of Zunyi Medical College, Guizhou Province, Zunyi City 563002, Peoples Republic of China
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  • Min Xu,

    1. Zunyi Hospital, The Third Affiliated Hospital of Zunyi Medical College, Guizhou Province, Zunyi City 563002, Peoples Republic of China
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  • Wenhui Zhang,

    1. Zunyi Hospital, The Third Affiliated Hospital of Zunyi Medical College, Guizhou Province, Zunyi City 563002, Peoples Republic of China
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  • Xiaole Wu,

    1. Zunyi Hospital, The Third Affiliated Hospital of Zunyi Medical College, Guizhou Province, Zunyi City 563002, Peoples Republic of China
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  • Jing Guan

    1. Zunyi Hospital, The Third Affiliated Hospital of Zunyi Medical College, Guizhou Province, Zunyi City 563002, Peoples Republic of China
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These authors contributed equally to the study.

To whom correspondence should be addressed (email yanglong1002@hotmail.com).

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.

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