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 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..
| Medienart: |
E-Artikel |
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| 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 - 80(2023), 8 vom: 18. Juli |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nivoit, Pierre [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| Themen: |
Autophagy |
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| Anmerkungen: |
© The Author(s) 2023. corrected publication 2023 |
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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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OLC2144498830 |
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| 520 | |a 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 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. | ||
| 650 | 4 | |a Autophagy | |
| 650 | 4 | |a Endothelium | |
| 650 | 4 | |a Flow-mediated dilatation | |
| 650 | 4 | |a Mechanosensing | |
| 650 | 4 | |a eNOS | |
| 650 | 4 | |a VEGFR2 | |
| 700 | 1 | |a Mathivet, Thomas |4 aut | |
| 700 | 1 | |a Wu, Junxi |4 aut | |
| 700 | 1 | |a Salemkour, Yann |4 aut | |
| 700 | 1 | |a Sankar, Devanarayanan Siva |4 aut | |
| 700 | 1 | |a Baudrie, Véronique |4 aut | |
| 700 | 1 | |a Bourreau, Jennifer |4 aut | |
| 700 | 1 | |a Guihot, Anne-Laure |4 aut | |
| 700 | 1 | |a Vessieres, Emilie |4 aut | |
| 700 | 1 | |a Lemitre, Mathilde |4 aut | |
| 700 | 1 | |a Bocca, Cinzia |4 aut | |
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| 700 | 1 | |a Lenoir, Olivia |0 (orcid)0000-0001-8107-6987 |4 aut | |
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