Autophagy protein 5 controls flow-dependent endothelial functions.
Langue
EN
Article de revue
Ce document a été publié dans
Cellular and Molecular Life Sciences. 2023-07-18, vol. 80, n° 8, p. 210
Résumé en anglais
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 ...Lire la suite >
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 and increased cerebral and renal vascular resistance in vivo. We found a crucial pathophysiological role for autophagy in endothelial cells 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 of autophagy in endothelial function, linking cell proteostasis to mechanosensing.< Réduire
Mots clés
Article recherche
Mots clés en anglais
Humans
Autophagy
Autophagy-Related Protein 5
Endothelial Cells
Endothelium
Vascular
Mesenteric Arteries
Myocardial Infarction
Nitric Oxide Synthase Type III
Signal Transduction
Vasodilation
Animals
Mice
Unités de recherche