1. eNOS-NO-induced small blood vessel relaxation requires EHD2-dependent caveolae stabilization
- Author
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Matthaeus, Claudia, Lian, Xiaoming, Kunz, Séverine, Lehmann, Martin, Zhong, Cheng, Bernert, Carola, Lahmann, Ines, Müller, Dominik N., Gollasch, Maik, and Daumke, Oliver
- 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 - 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.
- Published
- 2019