0141 : NmMLCK a key player in intermittent hypoxia-induced inflammatory vascular remodeling?

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• 作者：Claire Arnaud ; ¹ ; ^{claire.arnaud@ujf-grenoble.fr" class="auth_mail" title="E-mail the corresponding author} ; Sylvain Recoquillon² ; Sophie Bouyon¹ ; Sandrine Cachot¹ ; Emeline Lemarié ; ¹ ; Marta Toral² ; M. Carmen Martinez² ; Ramaroson Andriantsitohaina² ; Jean-Louis Pepin¹
• 刊名：Archives of Cardiovascular Diseases Supplements
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：8
• 期：3
• 页码：193
• 全文大小：51 K

文摘

Obstructive sleep apnea (OSA) is characterized by repetitive pharyngeal collapses during sleep leading to intermittent hypoxia (IH), the main contributor of OSA-related cardiovascular morbidity. OSA patients exhibit increased intima-media thickness (IMT) that correlates with circulating inflammatory markers and severity of nocturnal oxygen desaturation. In mice models, IH also induces hemodynamic alterations and cardiovascular inflammatory remodeling. The non-muscle myosin light chain kinase (nmMLCK) isoform contributes to endothelial cell-cell junction opening, monocyte migration and thus participates to inflammation. nmMLCK deficiency or inhibition has been reported to attenuate systemic, lung and atherosclerotic inflammation.

Objective

The aim of the present study was to investigate the role of nmMLCK in the IH-induced inflammatory vascular remodeling. We assess vascular remodeling/inflammation in different vascular beds (aorta, carotid and mesenteric arteries).

Methods and results

12 week-old C57bl6 or nmMLCK knockout mice were exposed to 14-days IH or normoxia. IH was associated with an elevation of mean arterial pressure, which was prevented by the nmMLCK deletion. We demonstrated that IH induced an inflammatory response in the three vascular beds, characterized by an increased mRNA expression of CD45 and IFNγ, an increased expression of the macrophage marker F4/80 and an increased expression and activity of NFkB. Interestingly nmMLCK deletion prevented the IH-induced vascular inflammatory responses. On-going experiments are characterizing the effect of nmMLCK deletion on IH-induced structural vascular remodeling.

Conclusions

These results strongly suggest that nmMLCK participates to IH-induced vascular inflammatory remodeling and might represent an attractive target to fight against the occurrence of inflammation and the vascular outcomes of OSA.

The author hereby declares no conflict of interest