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 |
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Erscheinungsjahr: |
2022 |
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Erschienen: |
2022 |
Enthalten in: |
ResearchSquare.com - (2022) vom: 05. Dez. Zur Gesamtaufnahme - year:2022 |
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Sprache: |
Englisch |
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Beteiligte Personen: |
Nivoit, Pierre [VerfasserIn] |
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Links: |
Volltext [kostenfrei] |
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Themen: |
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doi: |
10.21203/rs.3.rs-2276541/v1 |
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funding: |
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PPN (Katalog-ID): |
XRA038058510 |
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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, 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. | ||
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700 | 1 | |a Lemitre, Mathilde |e verfasserin |4 aut | |
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