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 |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:80 |
---|---|
Enthalten in: |
Cellular and molecular life sciences - 80(2023), 8 vom: 18. Juli |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Nivoit, Pierre [VerfasserIn] |
---|
Links: |
Volltext [kostenfrei] |
---|
Themen: |
Autophagy |
---|
Anmerkungen: |
© The Author(s) 2023. corrected publication 2023 |
---|
doi: |
10.1007/s00018-023-04859-9 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
SPR052271706 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | SPR052271706 | ||
003 | DE-627 | ||
005 | 20230906064705.0 | ||
007 | cr uuu---uuuuu | ||
008 | 230718s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1007/s00018-023-04859-9 |2 doi | |
035 | |a (DE-627)SPR052271706 | ||
035 | |a (SPR)s00018-023-04859-9-e | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Nivoit, Pierre |e verfasserin |4 aut | |
245 | 1 | 0 | |a Autophagy protein 5 controls flow-dependent endothelial functions |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a Computermedien |b c |2 rdamedia | ||
338 | |a Online-Ressource |b cr |2 rdacarrier | ||
500 | |a © The Author(s) 2023. corrected publication 2023 | ||
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 |7 (dpeaa)DE-He213 | |
650 | 4 | |a Endothelium |7 (dpeaa)DE-He213 | |
650 | 4 | |a Flow-mediated dilatation |7 (dpeaa)DE-He213 | |
650 | 4 | |a Mechanosensing |7 (dpeaa)DE-He213 | |
650 | 4 | |a eNOS |7 (dpeaa)DE-He213 | |
650 | 4 | |a VEGFR2 |7 (dpeaa)DE-He213 | |
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 | |
700 | 1 | |a Teillon, Jérémie |4 aut | |
700 | 1 | |a Le Gall, Morgane |4 aut | |
700 | 1 | |a Chipont, Anna |4 aut | |
700 | 1 | |a Robidel, Estelle |4 aut | |
700 | 1 | |a Dhaun, Neeraj |4 aut | |
700 | 1 | |a Camerer, Eric |4 aut | |
700 | 1 | |a Reynier, Pascal |4 aut | |
700 | 1 | |a Roux, Etienne |4 aut | |
700 | 1 | |a Couffinhal, Thierry |4 aut | |
700 | 1 | |a Hadoke, Patrick W. F. |4 aut | |
700 | 1 | |a Silvestre, Jean-Sébastien |4 aut | |
700 | 1 | |a Guillonneau, Xavier |4 aut | |
700 | 1 | |a Bonnin, Philippe |4 aut | |
700 | 1 | |a Henrion, Daniel |4 aut | |
700 | 1 | |a Dengjel, Joern |4 aut | |
700 | 1 | |a Tharaux, Pierre-Louis |4 aut | |
700 | 1 | |a Lenoir, Olivia |0 (orcid)0000-0001-8107-6987 |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Cellular and molecular life sciences |d Cham (ZG) : Springer International Publishing AG, 1997 |g 80(2023), 8 vom: 18. Juli |w (DE-627)SPR00008039X |w (DE-600)1458497-9 |x 1420-9071 |7 nnns |
773 | 1 | 8 | |g volume:80 |g year:2023 |g number:8 |g day:18 |g month:07 |
856 | 4 | 0 | |u https://dx.doi.org/10.1007/s00018-023-04859-9 |z kostenfrei |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_SPRINGER | ||
951 | |a AR | ||
952 | |d 80 |j 2023 |e 8 |b 18 |c 07 |