eNOS-NO-induced small blood vessel relaxation requires EHD2-dependent caveolae stabilization.
Animals
Blood Vessels
/ physiology
Calcium
/ metabolism
Carrier Proteins
/ metabolism
Caveolae
/ metabolism
Cell Membrane
/ metabolism
Cytosol
/ metabolism
Human Umbilical Vein Endothelial Cells
/ metabolism
Humans
Mesenteric Arteries
/ diagnostic imaging
Mice, Inbred C57BL
Nitric Oxide
/ metabolism
Nitric Oxide Synthase Type III
/ metabolism
Physical Conditioning, Animal
Vasodilation
/ physiology
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
18
06
2019
accepted:
24
09
2019
entrez:
11
10
2019
pubmed:
11
10
2019
medline:
12
3
2020
Statut:
epublish
Résumé
Endothelial nitric oxide synthase (eNOS)-related vessel relaxation is a highly coordinated process that regulates blood flow and pressure and is dependent on caveolae. Here, we investigated the role of caveolar plasma membrane stabilization by the dynamin-related ATPase EHD2 on eNOS-nitric oxide (NO)-dependent vessel relaxation. Loss of EHD2 in small arteries led to increased numbers of caveolae that were detached from the plasma membrane. Concomitantly, impaired relaxation of mesenteric arteries and reduced running wheel activity were observed in EHD2 knockout mice. EHD2 deletion or knockdown led to decreased production of nitric oxide (NO) although eNOS expression levels were not changed. Super-resolution imaging revealed that eNOS was redistributed from the plasma membrane to internalized detached caveolae in EHD2-lacking tissue or cells. Following an ATP stimulus, reduced cytosolic Ca2+ peaks were recorded in human umbilical vein endothelial cells (HUVECs) lacking EHD2. Our data suggest that EHD2-controlled caveolar dynamics orchestrates the activity and regulation of eNOS/NO and Ca2+ channel localization at the plasma membrane.
Identifiants
pubmed: 31600286
doi: 10.1371/journal.pone.0223620
pii: PONE-D-19-17247
pmc: PMC6786623
doi:
Substances chimiques
Carrier Proteins
0
EHD2 protein, human
0
EHD2 protein, mouse
0
Nitric Oxide
31C4KY9ESH
Nitric Oxide Synthase Type III
EC 1.14.13.39
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0223620Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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