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Archives of cardiovascular diseases
Volume 102, n° S1
page 8 (mars 2009)
Doi : 10.1016/S1875-2136(09)72139-4
Themes et posters

A006 Intermittent hypoxia induces inflammatory vascular and myocardial remodeling: role of the endothelin system
 

E. Belaidi 1, C. Arnaud 1, S. Cachot 1, P. Levy 1, 2, D. Godin-Ribuot 1
1 Inserm ERI17-Université Joseph Fourier-Faculté de Médecine IFR1, Grenoble, France 
2 CHU Hôpital A. Michallon-Laboratoire du sommeil et EFCR, Grenoble, France 

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Introduction

Obstructive sleep apnea (OSA) syndrome, characterized by intermittent hypoxia (IH), is associated with an increased cardiovascular morbidity that can be partially corrected by continuous positive airway pressure (CPAP) therapy. We have shown previously that IH induces increased aortic intima-media thickness (IMT) and NFkB activation. OSA patients also exhibit increased IMT that correlates with inflammatory markers and nocturnal oxygen desaturation. Endothelin release is promoted by hypoxia and ET-1 is known to exert potent pro-inflammatory and pro-mitogenic effects on the cardiovascular system.

Objective

The aim of the present study was to investigate the involvement of the endothelin system in IH-induced inflammatory vascular and myocardial remodeling.

Methods and Results

8 week-old C57bl6 mice (n=8 to 10 per group) were exposed 14 days to IH or normoxia (N). The role of the ET system was evaluated by treating the mice with the dual ET 1 receptor antagonist, bosentan (b: 100mg/kg/day in food) throughout the period of exposure. Myocardial big ET-1 levels were significantly increased by IH (p<0.01). Bosentan treatment significantly inhibited the IH-induced NFkB activity in both aorta (p<0.05) and myocardium (p<0.01). This was associated with prevention of IH-induced increase of aortic IMT and systemic inflammation.

Conclusions

These results demonstrate that the endothelin system is involved in IH-induced inflammatory vascular remodeling. Therefore, endothelin receptor blockade could represent a new therapeutic approach, in addition to CPAP therapy, for OSA patients prone to develop cardiovascular alterations. Further studies will investigate the link between transcriptional activity, ET-1 system, and inflammatory response in our conditions of hypoxia.

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