Résumé
Obstructive Sleep Apnea Syndrome (OSAS) is defined by repetitive obstructions of upper airway during sleep inducing intermittent decrease in oxygen saturation or intermittent hypoxia (IH). IH alters endothelial function favoring inflammation and could accelerate atherosclerosis-induced cardiovascular diseases. A protein that may play a role in this process is the nonmuscular myosin light chain kinase (nmMLCK), protein involved in the regulation of endothelial permeability. The aim of this study was to analyze the implication of nmMLCK in inflammation induced by IH on endothelial cells. Human aortic endothelial cells (HAoECs) were exposed to 6h of IH, including 30min of hypoxia (O2 5%) followed by 30min of normoxia (O2 21%), in absence or presence of ML-7 (5μM), a nmMLCK inhibitor, and in absence or presence of interleukin-6 (IL-6, 40ng/ml), an inflammatory cytokine found in OSAS patients. After stimulation, we investigated inflammatory process by evaluating p65-NF-κB pathway and the release of several inflammatory cytokines by HAoECs. Activation of p65-NF-κB inflammatory pathway is increased in response to IH, as well as secretion of certain inflammatory cytokines such as IL-6 and CXCL-1 in HAoECs. While nmMLCK inhibition by ML-7 did not prevent p65-NF-κB activation, it partially decreased IL-6 and CXCL-1 secretion induced by IH. Moreover, to mimic the pro-inflammatory environment already established in OSAS patients, we costimulated HAoECs with IL-6 and IH. Under these conditions, IL-6 alone increased activation of STAT3 but did not potentiate the effects of IH regarding p65-NF-κB activation and cytokine secretion. These results suggest that nmMLCK may participate to the IH-induced inflammatory process in endothelial cells by modulating IH-induced cytokine secretion. Furthermore, IH is sufficient to induce inflammatory process independently of the proinflammatory environment.
The author hereby declares no conflict of interest