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eNOS-NO-induced small blood vessel relaxation requires EHD2-dependent caveolae stabilization
- Source :
- PLoS ONE, PLoS ONE, Vol 14, Iss 10, p e0223620 (2019)
- Publication Year :
- 2019
- Publisher :
- Public Library of Science, 2019.
-
Abstract
- 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 Ca(2+) 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 Ca(2+) channel localization at the plasma membrane.
- Subjects :
- Cancer Research
Cell Membranes
Biochemistry
Cytosol
Medicine and Health Sciences
Small interfering RNAs
Staining
Cell Staining
Arteries
Animal Models
Mesenteric Arteries
Nucleic acids
Vasodilation
Experimental Organism Systems
Medicine
Cellular Structures and Organelles
Anatomy
Technology Platforms
Function and Dysfunction of the Nervous System
Research Article
Nitric Oxide Synthase Type III
Science
Mouse Models
Research and Analysis Methods
Caveolae
Nitric Oxide
Model Organisms
Physical Conditioning, Animal
Genetics
Human Umbilical Vein Endothelial Cells
Animals
Humans
Non-coding RNA
Cell Membrane
Biology and Life Sciences
Membrane Proteins
Cell Biology
Gene regulation
Mice, Inbred C57BL
Coated Pits
Specimen Preparation and Treatment
Cardiovascular and Metabolic Diseases
Cardiovascular Anatomy
Animal Studies
Blood Vessels
RNA
Calcium
Gene expression
Carrier Proteins
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- PLoS ONE, PLoS ONE, Vol 14, Iss 10, p e0223620 (2019)
- Accession number :
- edsair.pmid.dedup....283f6427939108aaa1280ee0b70ffc82