RRC ID 73678
Author 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
Title Autophagy protein 5 controls flow-dependent endothelial functions
Abstract 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.
DOI 10.21203/rs.3.rs-2276541/v1
PMID 37460898
PMC PMC10352428
MeSH Animals Autophagy Autophagy-Related Protein 5 / genetics Autophagy-Related Protein 5 / metabolism Endothelial Cells* / metabolism Endothelium, Vascular / metabolism Humans Mesenteric Arteries / metabolism Mice Myocardial Infarction* / metabolism Nitric Oxide Synthase Type III / metabolism Signal Transduction Vasodilation
Mice RBRC02975