Reduced endothelial dependent vasodilation in vessels from TLR4(-/-) mice is associated with increased superoxide generation
| العنوان: | Reduced endothelial dependent vasodilation in vessels from TLR4(-/-) mice is associated with increased superoxide generation |
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| المؤلفون: | Louise S. Harrington, Michael Waight, Jane A. Mitchell, Adrian Rozario, Martina H. Lundberg |
| المصدر: | Biochemical and Biophysical Research Communications |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | DAPI, 4′,6-diamidino-2-phenylinodole, U46619, 9,11-dideoxy-11α,9α-epoxymethanoprostaglandin F2α, Vasodilation, 030204 cardiovascular system & hematology, Biochemistry, chemistry.chemical_compound, Mice, 0302 clinical medicine, Superoxides, Vasoconstrictor Agents, Endothelial dysfunction, Mesenteric arteries, 0303 health sciences, biology, Superoxide, Nox, NADPH oxidase, Artery, Toll like receptor 4, Endothelial stem cell, medicine.anatomical_structure, PSS, physiological saline solution, SNP, sodium nitroprusside, Basal nitric oxide, lipids (amino acids, peptides, and proteins), Female, Dihydroethidium, Ach, acetylcholine, medicine.medical_specialty, Biophysics, Nitric Oxide, Article, Nitric oxide, Superoxide dismutase, 03 medical and health sciences, Internal medicine, SOD, superoxide dismutase, medicine, Animals, Molecular Biology, 030304 developmental biology, Endothelium-Dependent Relaxing Factors, TLR, Toll like receptor, Cell Biology, medicine.disease, Acetylcholine, Mice, Mutant Strains, Toll-Like Receptor 4, Endocrinology, chemistry, 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid, Immunology, biology.protein, Blood Vessels, Endothelium, Vascular, DHE, dihydroethidium, Myograph |
| الوصف: | Highlights ► The absence of TLR4 is associated with reduced endothelial cell function in mesenteric arteries. ► TLR4−/− mouse arteries have reduced acetylcholine responses. ► TLR4−/− have increased superoxide levels when stimulated with acetylcholine. ► An increase in superoxide generation reduces the activity of endothelial derived nitric oxide. Toll like receptor (TLR)4 is a pattern recognition receptor expressed in endothelial and other cells, responsible for the sensing of endotoxin and host derived ligands. Our group has shown previously that the absence of TLR4 is associated with reduced endothelial dependent vasodilator responses and left heart hypertrophy in animal models. However, the mechanism behind reduced endothelial cell function in TLR4−/− mice is not known. We have used en face confocal imaging of mesenteric arteries from mice deficient in the TLR4 receptor stained with dihydroethidium (DHE) to measure superoxide production. Using the isometric wire myograph, mesenteric artery vasodilator responses to acetylcholine and MnCl2 (a superoxide dismutase mimetic) were measured. Mesenteric arteries from TLR4−/− mice had a reduced endothelial dependent relaxant response and increased superoxide levels when stimulated with acetylcholine. Increased levels of superoxide, as detected by DHE staining, were seen in vessels from TLR4−/− mice, which were reduced to control levels in the presence of MnCl2. Our observations suggest that loss of TLR4 increases superoxide generation which reduces the biological activity of endothelial derived nitric oxide and thereby explains the endothelial dysfunction and associated cardiovascular phenotype in TLR4−/− mice. These data implicate a novel cardio-protective role for TLR4 in vascular homeostasis. |
| تدمد: | 1090-2104 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4405e2b50473c0ea26276b5c9a2da899Test https://pubmed.ncbi.nlm.nih.gov/21513697Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4405e2b50473c0ea26276b5c9a2da899 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10902104 |
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