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PTEN inhibition enhances angiogenesis in an in vitro model of ischemic injury by promoting Akt phosphorylation and subsequent hypoxia inducible factor-1α upregulation

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Abstract

Angiogenesis is an important pathophysiological response to cerebral ischemia. PTEN is a lipid phosphatase whose loss activates PI3K/Akt signaling, which is related to HIF-1α upregulation and enhanced angiogenesis in human cancer cells. However, the specific roles of PTEN in endothelial cell functions and angiogenesis after cerebral ischemia remain unknown. Therefore, we sought to examine the potential effects of PTEN inhibition on post-ischemic angiogenesis in human blood vessel cells and to determine the underlying mechanism. In this present study, human umbilical vein endothelial cells (HUVECs) were exposed to oxygen-glucose deprivation (OGD), cell proliferation, migration and apoptosis, in vitro tube formation and expression of PTEN/Akt pathway and angiogenic factors were examined in HUVECs after treatment with PTEN inhibitor bisperoxovanadium (bpV) at different doses. The results showed that bpV significantly increased the cell proliferation and reduced cell apoptosis indicating that the drug exerts a cytoprotective effect on HUVECs with OGD exposure. bpV also enhanced cell migration and tube formation in HUVECs following OGD, and upregulated HIF-1α and VEGF expressions, but attenuated endostatin expression. Additionally, western blotting analysis demonstrated that Akt phosphorylation in HUVECs was significantly increased after bpV treatment. These findings suggest that PTEN inhibition promotes post-ischemic angiogenesis in HUVECs after exposure to OGD and this enhancing effect might be achieved through activation of the Akt signal cascade.

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Acknowledgments

This study was supported by National Natural Science Foundation of China (81501657) and Shanghai Jiao Tong University Affiliated Sixth People’s Hospital Foundation (LYZY-0101).

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Authors and Affiliations

  1. Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People′s Hospital, Shanghai, China

    Lixia Xue, Jiankang Huang, Ting Zhang, Xiuzhe Wang, Jianliang Fu, Zhi Geng & Yuwu Zhao

  2. Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People′s Hospital, 600 Yishan Road, Xuhui District, Shanghai, 20033, China

    Hao Chen

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  1. Lixia Xue
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  2. Jiankang Huang
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  3. Ting Zhang
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  4. Xiuzhe Wang
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  7. Yuwu Zhao
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  8. Hao Chen
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Correspondence to Hao Chen.

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Xue, L., Huang, J., Zhang, T. et al. PTEN inhibition enhances angiogenesis in an in vitro model of ischemic injury by promoting Akt phosphorylation and subsequent hypoxia inducible factor-1α upregulation. Metab Brain Dis 33, 1679–1688 (2018). https://doi.org/10.1007/s11011-018-0276-5

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  • DOI: https://doi.org/10.1007/s11011-018-0276-5

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