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Nature, Cell Metabolism Novel discoveries on endothelial cell metabolism in angiogenesis

By Dr. Xuri Li from Zhongshan Ophthalmic Center, Sun Yat-Sen University

and Dr. Peter Carmeliet from VIB-KU-Leuven, Belgium


On August 29, 2018, an article titled “Role of glutamine synthetase in angiogenesis beyond glutamine synthesis” was published by the journal of Nature. In this article, Dr. Xuri Li at the Zhongshan Ophthalmic Center (ZOC), Sun Yat-Sen University (SYSU) and Dr. Peter Carmeliet at VIB-KU Leuven in Belgium reveal a previously unrecognized novel role of glutamine synthetase in angiogenesis by promoting vascular endothial cell migration via sustaining RHOJ palmitoylation, membrane localization and activation1.


                     

 

Glutamine synthetase (GS) is an enzyme that converts glutamate and ammonia to glutamine. Although highly expressed in endothelial cells, it’s role in vessel growth remained unknown. In this work, Dr. Li and Dr. Carmeliet elucidate that deletion of the gene encoding GS impairs vessel sprouting during mouse development, and pharmacological inhibition of GS suppresses angiogenesis in ocular and inflammatory skin diseases by halting endothelial cell migraton. Importantly, while supressing pathological angiogenesis, blocking GS minimally affected normal blood vessels, demonstrating a valuable safty profile for anti-angiogenic therapy. Thus, manipulating GS activity may shed new light into the treatment of neovacular diseases.

 

Glutamine synthetase (GS) is an enzyme that converts glutamate and ammonia to glutamine. Although highly expressed in endothelial cells, it’s role in vessel growth remained unknown. In this work, Dr. Li and Dr. Carmeliet elucidate that deletion of the gene encoding GS impairs vessel sprouting during mouse development, and pharmacological inhibition of GS suppresses angiogenesis in ocular and inflammatory skin diseases by halting endothelial cell migraton. Importantly, while supressing pathological angiogenesis, blocking GS minimally affected normal blood vessels, demonstrating a valuable safty profile for anti-angiogenic therapy. Thus, manipulating GS activity may shed new light into the treatment of neovacular diseases.