• Research

Nonmuscle Myosin Light Chain Kinase: A Key Player in Intermittent Hypoxia-Induced Vascular Alterations. J Am Heart Assoc. 2018 Jan 25;7(3). pii: e007893

Arnaud C, Bouyon S, Recoquillon S, Brasseur S, Lemarié E, Briançon-Marjollet A, Gonthier B, Toral M, Faury G, Martinez MC, Andriantsitohaina R, Pepin JL
doi : 10.1161/JAHA.117.007893
http://jaha.ahajournals.org/content/7/3/e007893


Abstract

Background: Obstructive sleep apnea is characterized by repetitive pharyngeal collapses during sleep, leading to intermittent hypoxia (IH), the main contributor of obstructive sleep apnea–related cardiovascular morbidity. In patients and rodents with obstructive sleep apnea exposed to IH, vascular inflammation and remodeling, endothelial dysfunction, and circulating inflammatory markers are linked with IH severity. The nonmuscle myosin light chain kinase (nmMLCK) isoform contributes to vascular inflammation and oxidative stress in different cardiovascular and inflammatory diseases. Thus, in the present study, we hypothesized that nmMLCK plays a key role in the IH?induced vascular dysfunctions and inflammatory remodeling.
Methods and Results: Twelve?week?old nmMLCK+/+ or nmMLCK?/? mice were exposed to 14?day IH or normoxia. IH was associated with functional alterations characterized by an elevation of arterial blood pressure and stiffness and perturbations of NO signaling. IH caused endothelial barrier dysfunction (ie, reduced transendothelial resistance in vitro) and induced vascular oxidative stress associated with an inflammatory remodeling, characterized by an increased intima?media thickness and an increased expression and activity of inflammatory markers, such as interferon?? and nuclear factor??B, in the vascular wall. Interestingly, nmMLCK deletion prevented all IH?induced functional and structural alterations, including the restoration of NO signaling, correction of endothelial barrier integrity, and reduction of both oxidative stress and associated inflammatory response.
Conclusions: nmMLCK is a key mechanism in IH?induced vascular oxidative stress and inflammation and both functional and structural remodeling.



Published on August 23, 2018