2026-06-14T05:04:51Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/85412024-09-27T10:02:13Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Gomez-Escudero, Jesus author Clemente, Cristina author García-Weber, Diego author Acin-Perez, Rebeca author Millán, Jaime author Enriquez, Jose Antonio author Bentley, Katie author Carmeliet, Peter author Arroyo, Alicia G author 2019-10 Angiogenesis, the formation of new blood vessels from pre-existing ones, occurs in pathophysiological contexts such as wound healing, cancer, and chronic inflammatory disease. During sprouting angiogenesis, endothelial tip and stalk cells coordinately remodel their cell-cell junctions to allow collective migration and extension of the sprout while maintaining barrier integrity. All these processes require energy, and the predominant ATP generation route in endothelial cells is glycolysis. However, it remains unclear how ATP reaches the plasma membrane and intercellular junctions. In this study, we demonstrate that the glycolytic enzyme pyruvate kinase 2 (PKM2) is required for sprouting angiogenesis in vitro and in vivo through the regulation of endothelial cell-junction dynamics and collective migration. We show that PKM2-silencing decreases ATP required for proper VE-cadherin internalization/traffic at endothelial cell-cell junctions. Our study provides fresh insight into the role of ATP subcellular compartmentalization in endothelial cells during angiogenesis. Since manipulation of EC glycolysis constitutes a potential therapeutic intervention route, particularly in tumors and chronic inflammatory disease, these findings may help to refine the targeting of endothelial glycolytic activity in disease. Sci Rep. 2019; 9(1):15022 10.1038/s41598-019-50866-x 2045-2322 2045-2322 Scientific reports 31636306 http://hdl.handle.net/20.500.12105/8541 PKM2 regulates endothelial cell junction dynamics and angiogenesis via ATP production