論文 - 詳細
| RRC ID | 73678 |
|---|---|
| 著者 | Pierre Nivoit, Thomas Mathivet, Junxi Wu, Yann Salemkour, Devanarayanan Siva Sankar, Véronique Baudrie, Jennifer Bourreau, Anne-Laure Guihot, Emilie Vessières, Mathilde Lemitre, Cinzia Bocca, Jérémie Teillon, Morgane Le Gall, Anna Chipont, Estelle Robidel, Neeraj Dhaun, Eric Camerer, Pascal Reynier, Etienne Roux, Thierry Couffinhal, Patrick Hadoke, Jean-sébastien Silvestre, Xavier Guillonneau, Philippe Bonnin, Daniel Henrion, Jörn Dengjel, Pierre-Louis Tharaux, Olivia Lenoir |
| タイトル | 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. |
| DOI | 10.21203/rs.3.rs-2276541/v1 |
| PMID | 37460898 |
| PMC | PMC10352428 |
| MeSH | Animals Autophagy Autophagy-Related Protein 5 / genetics Autophagy-Related Protein 5 / metabolism Endothelial Cells* / metabolism Endothelium, Vascular / metabolism Humans Mesenteric Arteries / metabolism Mice Myocardial Infarction* / metabolism Nitric Oxide Synthase Type III / metabolism Signal Transduction Vasodilation |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 14 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC02975 |