The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Endothelial PFKFB3 Plays a Critical Role in Angiogenesis
Open accessAbstract
Objective—: Vascular cells, particularly endothelial cells, adopt aerobic glycolysis to generate energy to support cellular functions. The effect of endothelial glycolysis on angiogenesis remains unclear. 6-Phosphofructo-2-kinase/fructose-2, 6-bisphosphatase, isoform 3 (PFKFB3) is a critical enzyme for endothelial glycolysis. By blocking or deleting PFKFB3 in endothelial cells, we investigated the influence of endothelial glycolysis on angiogenesis both in vitro and in vivo. Approach and Results—: Under hypoxic conditions or after treatment with angiogenic factors, endothelial PFKFB3 was upregulated both in vitro and in vivo. The knockdown or overexpression of PFKFB3 suppressed or accelerated endothelial proliferation and migration in vitro, respectively. Neonatal mice from a model of oxygen-induced retinopathy showed suppressed neovascular growth in the retina when endothelial PFKFB3 was genetically deleted or when the mice were treated with a PFKFB3 inhibitor. In addition, tumors implanted in mice deficient in endothelial PFKFB3 grew more slowly and were provided with less blood flow. A lower level of phosphorylated protein kinase B was observed in PFKFB3-knockdown endothelial cells, which was accompanied by a decrease in intracellular lactate. The addition of lactate to PFKFB3-knockdown cells rescued the suppression of endothelial proliferation and migration. Conclusions—: The blockade or deletion of endothelial PFKFB3 decreases angiogenesis both in vitro and in vivo. Thus, PFKFB3 is a promising target for the reduction of endothelial glycolysis and its related pathological angiogenesis.
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Cites
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Molecular mechanisms and clinical applications of angiogenesis
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Cited by
Glycolysis – a key player in the inflammatory response
Soto‐Heredero, G., Gómez de las Heras, M. M., Gabandé‐Rodríguez, E., Oller, J., & Mittelbrunn, M. (2020) · The FEBS Journal · doi:10.1111/febs.15327 · Cited by 641
Glycolytic Reprogramming in Myofibroblast Differentiation and Lung Fibrosis
Xie, N., Tan, Z., Banerjee, S., Cui, H., Ge, J., Liu, R.-M., Bernard, K., Thannickal, V. J., & Liu, G. (2015) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201504-0780oc · Cited by 582
Eelen, G., de Zeeuw, P., Treps, L., Harjes, U., Wong, B. W., & Carmeliet, P. (2018) · Physiological Reviews · doi:10.1152/physrev.00001.2017 · Cited by 572
Zhang, J., Muri, J., Fitzgerald, G., Gorski, T., Gianni-Barrera, R., Masschelein, E., D’Hulst, G., Gilardoni, P., Turiel, G., Fan, Z., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.05.004 · Cited by 533
Targeting metabolic dysregulation for fibrosis therapy
Zhao, X., Kwan, J. Y. Y., Yip, K., Liu, P. P., & Liu, F.-F. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0040-5 · Cited by 513
Metadata
- Authors
- Xu, Y., An, X., Guo, X., Habtetsion, T. G., Wang, Y., Xu, X., Kandala, S., Li, Q., Li, H., Zhang, C., Caldwell, R. B., Fulton, D. J., Su, Y., Hoda, M. N., Zhou, G., Wu, C., & Huo, Y.
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2014-06
- Volume
- 34
- Issue
- 6
- Pages
- 1231-1239
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2060824010
- Cited by
- 248
- References
- 8
- FWCI
- 6.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Endothelial PFKFB3 Plays a Critical Role in Angiogenesis. https://app.cochat.ai/papers/10.1161/atvbaha.113.303041
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- Xu, Y., An, X., Guo, X., Habtetsion, T. G., Wang, Y., Xu, X., Kandala, S., Li, Q., Li, H., Zhang, C., Caldwell, R. B., Fulton, D. J., Su, Y., Hoda, M. N., Zhou, G., Wu, C., & Huo, Y. (2014). Endothelial PFKFB3 Plays a Critical Role in Angiogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology. https://doi.org/10.1161/atvbaha.113.303041
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