@misc{10481/56307,
year = {2017},
month = {10},
url = {http://hdl.handle.net/10481/56307},
abstract = {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.},
organization = {S.R. is a recipient of doctoral fellowships from the French Education Ministry, Société Française de Cardiologie and Groupe de Réflexion sur la Recherche Cardiovasculaire. This work is partially supported by Agence Nationale de la Recherche (ANR-12-BSV1-0024-01), Université d’Angers, INSERM and Campus France.},
publisher = {Springer Nature},
keywords = {Non-muscular myosin light chain kinase},
keywords = {nmMLCK},
keywords = {intermittent hypoxia},
keywords = {OSA},
keywords = {endothelial dysfunction},
keywords = {Obstructive sleep apnea},
keywords = {ML-7},
title = {Non-muscular myosin light chain kinase triggers intermittent hypoxia-induced interleukin-6 release, endothelial dysfunction and permeability},
doi = {10.1038/s41598-017-13268-5},
author = {Gómez Guzmán, Manuel and Recoquillon, Sylvain and Rodier, Marion and Koffi, Camille and Nitiéma, Mathieu and Gagnadoux, Frédéric and Martínez, M. Carmen and Andriantsitohaina, Ramaroson},
}