Autophagy protein 5 controls flow-dependent endothelial functions
© 2023. The Author(s)..
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.
| Errataetall: |
ErratumIn: Cell Mol Life Sci. 2023 Sep 4;80(9):275. - PMID 37665375 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:80 |
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| Enthalten in: |
Cellular and molecular life sciences : CMLS - 80(2023), 8 vom: 18. Juli, Seite 210 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nivoit, Pierre [VerfasserIn] |
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| Links: |
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| Themen: |
Autophagy |
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| Anmerkungen: |
Date Completed 24.07.2023 Date Revised 05.09.2023 published: Electronic ErratumIn: Cell Mol Life Sci. 2023 Sep 4;80(9):275. - PMID 37665375 Citation Status MEDLINE |
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| doi: |
10.1007/s00018-023-04859-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 500 | |a ErratumIn: Cell Mol Life Sci. 2023 Sep 4;80(9):275. - PMID 37665375 | ||
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| 520 | |a © 2023. The Author(s). | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Wu, Junxi |e verfasserin |4 aut | |
| 700 | 1 | |a Salemkour, Yann |e verfasserin |4 aut | |
| 700 | 1 | |a Sankar, Devanarayanan Siva |e verfasserin |4 aut | |
| 700 | 1 | |a Baudrie, Véronique |e verfasserin |4 aut | |
| 700 | 1 | |a Bourreau, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a Guihot, Anne-Laure |e verfasserin |4 aut | |
| 700 | 1 | |a Vessieres, Emilie |e verfasserin |4 aut | |
| 700 | 1 | |a Lemitre, Mathilde |e verfasserin |4 aut | |
| 700 | 1 | |a Bocca, Cinzia |e verfasserin |4 aut | |
| 700 | 1 | |a Teillon, Jérémie |e verfasserin |4 aut | |
| 700 | 1 | |a Le Gall, Morgane |e verfasserin |4 aut | |
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