Non-muscular myosin light chain kinase triggers intermittent hypoxia-induced interleukin-6 release, endothelial dysfunction and permeability Gómez Guzmán, Manuel Recoquillon, Sylvain Rodier, Marion Koffi, Camille Nitiéma, Mathieu Gagnadoux, Frédéric Martínez, M. Carmen Andriantsitohaina, Ramaroson Non-muscular myosin light chain kinase nmMLCK intermittent hypoxia OSA endothelial dysfunction Obstructive sleep apnea ML-7 Obstructive 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. 2019-07-05T09:22:54Z 2019-07-05T09:22:54Z 2017-10-20 info:eu-repo/semantics/article Recoquillon S, Gómez-Guzmán M, Rodier M, Koffi C, Nitiéma M, Gagnadoux F, Martínez MC, Andriantsitohaina R. Non-muscular myosin light chain kinase triggers intermittent hypoxia-induced interleukin-6 release, endothelial dysfunction and permeability. Sci Rep. 2017 Oct 20;7(1):13664. doi: 10.1038/s41598-017-13268-5. http://hdl.handle.net/10481/56307 10.1038/s41598-017-13268-5 eng http://creativecommons.org/licenses/by-nc-nd/3.0/es/ info:eu-repo/semantics/openAccess Atribución-NoComercial-SinDerivadas 3.0 España Springer Nature