Vascular endothelial growth factor signaling requires glycine to promote angiogenesis

Dongqing Guo, Colin E. Murdoch, Hao Xu, Hui Shi, Dayue Darrel Duan, Asif Ahmed, Yuchun Gu

    Research output: Contribution to journalArticlepeer-review

    39 Citations (Scopus)
    249 Downloads (Pure)

    Abstract

    Peripheral vascular occlusive disease (PVOD) is a common manifestation of atherosclerosis, and it has a high rate of morbidity. Therapeutic angiogenesis would re-establish blood perfusion and rescue ischemic tissue. Vascular endothelial growth factor (VEGF) induces angiogenesis and can potentially be used to treat ischemic diseases, yet in clinical trials VEGF has not fulfilled its full potential with side effects. Whether amino acids promote angiogenesis and the molecular mechanisms are largely unknown. Here we showed that (1) Glycine significantly promoted angiogenesis both in vitro and in vivo and effectively protected mitochondrial function. (2) Activation of glycine transporter 1(GlyT1) induced by VEGF led to an increase in intracellular glycine. (3) Glycine directly bounded to voltage dependent anion channel 1 (VDAC1) on the mitochondrial outer membrane and inhibited its opening. These original results highlight glycine as a necessary mediator in VEGF signalling via the GlyT1-glycine-mTOR-VDAC1 axis pathway. Therefore, the findings in this study are of significance providing new mechanistic insights into angiogenesis and providing better understanding of glycine function in angiogenesis, which may provide valuable information for development of novel therapeutic targets for the treatment of angiogenic vascular disorders.
    Original languageEnglish
    Pages (from-to)14749
    Number of pages1
    JournalScientific Reports
    Volume7
    Issue number1
    DOIs
    Publication statusPublished - 7 Nov 2017

    Keywords

    • Cell signalling
    • Mechanisms of disease

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