The DOI matches its Crossref record; 69 of the 69 references it cites were found in a registry or an index.
Amino Acid Restriction Triggers Angiogenesis via GCN2/ATF4 Regulation of VEGF and H2S Production
Open accessAbstract
Summary Angiogenesis, the formation of new blood vessels by endothelial cells (EC), is an adaptive response to oxygen/nutrient deprivation orchestrated by vascular endothelial growth factor (VEGF) upon ischemia or exercise. Hypoxia is the best-understood trigger of VEGF expression via the transcription factor HIF1α. Nutrient deprivation is inseparable from hypoxia during ischemia, yet its role in angiogenesis is poorly characterized. Here, we identified sulfur amino acid restriction as a proangiogenic trigger, promoting increased VEGF expression, migration and sprouting in EC in vitro, and increased capillary density in mouse skeletal muscle in vivo, via the GCN2/ATF4 amino acid starvation response pathway independent of hypoxia or HIF1α. We also identified a requirement for cystathionine-γ-lyase in VEGF-dependent angiogenesis via increased hydrogen sulfide (H2S) production. H2S mediated its proangiogenic effects in part by inhibiting mitochondrial electron transport and oxidative phosphorylation, resulting in increased glucose uptake and glycolytic ATP production.
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Cites
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VEGF receptor signalling ? in control of vascular function
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H 2 S as a Physiologic Vasorelaxant: Hypertension in Mice with Deletion of Cystathionine γ-Lyase
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Self-citationCaloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys
Colman, R. J., Anderson, R. M., Johnson, S. C., Kastman, E. K., Kosmatka, K. J., Beasley, T. M., Allison, D. B., Cruzen, C., Simmons, H. A., Kemnitz, J. W., et al. (2009) · Science · doi:10.1126/science.1173635 · Cited by 2,277
Hydrogen sulphide and its therapeutic potential
Szabó, C. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2425 · Cited by 2,038
Physiological Implications of Hydrogen Sulfide: A Whiff Exploration That Blossomed
Wang, R. (2012) · Physiological Reviews · doi:10.1152/physrev.00017.2011 · Cited by 1,939
Self-citationRole of PFKFB3-Driven Glycolysis in Vessel Sprouting
De Bock, K., Georgiadou, M., Schoors, S., Kuchnio, A., Wong, B. W., Cantelmo, A. R., Quaegebeur, A., Ghesquière, B., Cauwenberghs, S., Eelen, G., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.037 · Cited by 1,551
The role of nitric oxide in tumour progression
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H 2 S Signals Through Protein S-Sulfhydration
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Cited by
The integrated stress response: From mechanism to disease
Costa-Mattioli, M., & Walter, P. (2020) · Science · doi:10.1126/science.aat5314 · Cited by 1,617
The hallmarks of cancer metabolism: still emerging
Pavlova, N. N., Zhu, J., & Thompson, C. B. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.01.007 · Cited by 1,418
Impairment of an endothelial NAD(+)-H2S signaling network is a reversible cause of vascular aging
Das, A., Huang, G. X., Bonkowski, M. S., Longchamp, A., Li, C., Schultz, M. B., Kim, L.-J., Osborne, B., Joshi, S., Lu, Y., et al. (2018) · Cell · doi:10.1016/j.cell.2018.02.008 · Cited by 496
“It increases SIRT1 activity, protects against oxidative stress, and can promote angiogenesis (Longchamp et al., 2018).”
Self-citationEndothelial cell metabolism in cardiovascular physiology and disease
Pasut, A., Lama, E., Van Craenenbroeck, A. H., Kroon, J., & Carmeliet, P. (2025) · Nature Reviews Cardiology · doi:10.1038/s41569-025-01162-x · Cited by 74
The role of exercise-induced myokines in promoting angiogenesis
Qi, C., Song, X., Wang, H., Yan, Y., & Liu, B. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.981577 · Cited by 63
“It is reported that exercise can promote angiogenesis in the skeletal muscle, myocardium, and brain (Morland et al., 2017; Longchamp et al., 2018; Tryfonos et al., 2021).”
Background
Metadata
- Authors
- Longchamp, A., Mirabella, T., Arduini, A., MacArthur, M. R., Das, A., Treviño-Villarreal, J. H., Hine, C., Ben-Sahra, I., Knudsen, N. H., Brace, L. E., Reynolds, J., Mejia, P., Tao, M., Sharma, G., Wang, R., Corpataux, J.-M., Haefliger, J.-A., Ahn, K. H., Lee, C.-H., Manning, B. D., Sinclair, D. A., Chen, C. S., Ozaki, C. K., & Mitchell, J. R.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 173
- Issue
- 1
- Pages
- 117-129.e14
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2792937385
- Cited by
- 325
- References
- 69
- FWCI
- 10.75
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Amino Acid Restriction Triggers Angiogenesis via GCN2/ATF4 Regulation of VEGF and H2S Production. https://app.cochat.ai/papers/10.1016/j.cell.2018.03.001
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- Longchamp, A., Mirabella, T., Arduini, A., MacArthur, M. R., Das, A., Treviño-Villarreal, J. H., Hine, C., Ben-Sahra, I., Knudsen, N. H., Brace, L. E., Reynolds, J., Mejia, P., Tao, M., Sharma, G., Wang, R., Corpataux, J.-M., Haefliger, J.-A., Ahn, K. H., Lee, C.-H., . . . Mitchell, J. R. (2018). Amino Acid Restriction Triggers Angiogenesis via GCN2/ATF4 Regulation of VEGF and H2S Production. Cell. https://doi.org/10.1016/j.cell.2018.03.001
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
