Recoquillon, SylvainGómez-Guzmán, ManuelRodier, MarionKoffi, CamilleNitiéma, MathieuGagnadoux, FrédéricMartínez, M CarmenAndriantsitohaina, Ramaroson2025-01-072025-01-072017-10-20https://hdl.handle.net/10668/25490Obstructive sleep apnea is characterized by intermittent hypoxia (IH) which alters endothelial function, induces inflammation and accelerates atherosclerosis-induced cardiovascular diseases. The non-muscular myosin light chain kinase (nmMLCK) isoform contributes to endothelial cell-cell junction opening. Deletion of nmMLCK protects mice from death in septic shock models and prevents atherosclerosis in high-fat diet-fed mice. The aim of the study was to analyze the implication of nmMLCK in IH-induced vascular inflammation. Human aortic endothelial cells were exposed to 6 hours of IH in absence or presence of nmMLCK inhibitors, ML-7 (5 µM) or PIK (150 µM). IH increased reactive oxygen species (ROS) and nitric oxide (NO) production, p65-NFκB activation and IL-6 secretion. While nmMLCK inhibition did not prevent IH-induced ROS production and p65-NFκB activation, it decreased NO production and partially prevented IL-6 secretion. IH-induced IL-6 secretion and vesicle-associated membrane protein-associated vesicles re-organization were inhibited in presence of the inhibitor of protein secretion, brefeldin A, or ML-7. IH increased monocytes transendothelial migration that was partially prevented by ML-7. Finally, IH reduced endothelium-dependent relaxation to acetylcholine of aortas from wild-type but not those taken from nmMLCK-deficient mice. These results suggest that nmMLCK participates to IH-induced endothelial dysfunction resulting from cytokines secretion and endothelial permeability.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/AnimalsAortaAtherosclerosisCapillary PermeabilityCell AdhesionCell HypoxiaCell MovementCells, CulturedCoculture TechniquesDisease Models, AnimalEndothelial CellsHumansInterleukin-6Mice, KnockoutMyosin-Light-Chain KinaseReactive Oxygen SpeciesSecretory VesiclesSleep Apnea, ObstructiveTranscription Factor RelAresearch article29057883open access10.1038/s41598-017-13268-52045-2322PMC5651916https://www.nature.com/articles/s41598-017-13268-5.pdfhttps://pmc.ncbi.nlm.nih.gov/articles/PMC5651916/pdf