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..

Medienart:

Preprint

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

ResearchSquare.com - (2022) vom: 05. Dez. Zur Gesamtaufnahme - year:2022

Sprache:

Englisch

Beteiligte Personen:

Nivoit, Pierre [VerfasserIn]
Mathivet, Thomas [VerfasserIn]
Wu, Junxi [VerfasserIn]
Salemkour, Yann [VerfasserIn]
Sankar, Devanarayanan Siva [VerfasserIn]
Baudrie, Véronique [VerfasserIn]
Bourreau, Jennifer [VerfasserIn]
Guihot, Anne-Laure [VerfasserIn]
Vessières, Emilie [VerfasserIn]
Lemitre, Mathilde [VerfasserIn]
Bocca, Cinzia [VerfasserIn]
Teillon, Jérémie [VerfasserIn]
Gall, Morgane Le [VerfasserIn]
Chipont, Anna [VerfasserIn]
Robidel, Estelle [VerfasserIn]
Dhaun, Neeraj [VerfasserIn]
Camerer, Eric [VerfasserIn]
Reynier, Pascal [VerfasserIn]
Roux, Etienne [VerfasserIn]
Couffinhal, Thierry [VerfasserIn]
Hadoke, Patrick [VerfasserIn]
Silvestre, Jean-sébastien [VerfasserIn]
Guillonneau, Xavier [VerfasserIn]
Bonnin, Philippe [VerfasserIn]
Henrion, Daniel [VerfasserIn]
Dengjel, Jörn [VerfasserIn]
Tharaux, Pierre-Louis [VerfasserIn]
Lenoir, Olivia [VerfasserIn]

Links:

Volltext [kostenfrei]

Themen:

570
Biology

doi:

10.21203/rs.3.rs-2276541/v1

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

XRA038058510