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.
Bibliographical note© The Author(s) 2017. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Funding: Fundamental Research Funds of Beijing University of Chinese Medicine held by DG (No. 2017-JYB-JS-017); grants held by YG (973 Project No. 2013CB531206, 973 Project No. 2012CB517803 and NSF No. 81170236, No. 31127001, No. 81570245 and No. 31221002); and programme grant held by AA with Medical Research Council (G0700288) in addition to charitable support from Sir Doug Ellis and Dr Tim Watts (Pertemps) to Aston Medical School). Colin E Murdoch is an International Incoming Fellow and was supported by EU Framework 7 Marie Curie Fellowship (IVSCP-626633) is also a recipient of Diabetes UK Grant (16/0005453).
- Cell signalling, Mechanisms of disease
Guo, D., Murdoch, C. E., Xu, H., Shi, H., Duan, D. D., Ahmed, A., & Gu, Y. (2017). Vascular endothelial growth factor signaling requires glycine to promote angiogenesis. Scientific Reports, 7(1), 14749. https://doi.org/10.1038/s41598-017-15246-3