Autophagy protein 5 controls flow-dependent endothelial functions.
Autophagy
Endothelium
Flow-mediated dilatation
Mechanosensing
VEGFR2
eNOS
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
18 Jul 2023
18 Jul 2023
Historique:
received:
19
12
2022
accepted:
04
07
2023
revised:
28
06
2023
medline:
19
7
2023
pubmed:
18
7
2023
entrez:
17
7
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37460898
doi: 10.1007/s00018-023-04859-9
pii: 10.1007/s00018-023-04859-9
pmc: PMC10352428
doi:
Substances chimiques
Autophagy-Related Protein 5
0
Nitric Oxide Synthase Type III
EC 1.14.13.39
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
210Subventions
Organisme : European Research Council
ID : 107037
Pays : International
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2023. The Author(s).
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