| Autor: |
Pierre Nivoit, Thomas Mathivet, Junxi Wu, Yann Salemkour, Devanarayanan Siva Sankar, Véronique Baudrie, Jennifer Bourreau, Anne-Laure Guihot, Emilie Vessières, Mathilde Lemitre, Cinzia Bocca, Jérémie Teillon, Morgane Le Gall, Anna Chipont, Estelle Robidel, Neeraj Dhaun, Eric Camerer, Pascal Reynier, Etienne Roux, Thierry Couffinhal, Patrick Hadoke, Jean-sébastien Silvestre, Xavier Guillonneau, Philippe Bonnin, Daniel Henrion, Jörn Dengjel, Pierre-Louis Tharaux, Olivia Lenoir |
| Rok vydání: |
2022 |
| Popis: |
Dysregulated autophagy is associated with cardiovascular and metabolic diseases, where impaired flow-mediated endothelial cell responses promote cardiovascular risk. The mechanism by which the autophagy machinery regulates endothelial functions is complex. We applied multi-omics approaches and in vitro and in vivo functional assays to decipher the diverse roles of autophagy in endothelial cells. We demonstrate that autophagy regulates VEGF-dependent VEGFR signaling and VEGFR-mediated and flow-mediated eNOS activation. Endothelial ATG5 deficiency in vivo results in selective loss of flow-induced vasodilation in mesenteric arteries and kidneys, along with increased cerebral and renal vascular resistance. We found a crucial pathophysiological role for endothelial autophagy in flow-mediated outward arterial remodeling, prevention of neointima formation following wire injury, and recovery after myocardial infarction. Together, these findings unravel a fundamental role for autophagy in endothelial function, linking cell proteostasis to mechanosensing. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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