2026-06-16T14:04:05Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/85412024-09-27T10:02:13Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
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
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Knut and Alice Wallenberg Foundation
funder
Instituto de Salud Carlos III
funder
Fundación ProCNIC
2019-10-31T11:00:04Z
2019-10-31T11:00:04Z
2019-10
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
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.
eng
PKM2 regulates endothelial cell junction dynamics and angiogenesis via ATP production
journal article
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