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Microparticles from OSA patients induce hyper-reactivity through up-regulation of pro-inflammatory proteins

Simon Tual-Chalot, Keita Fatoumata, Pascaline Priou, Wojciech Trzepizur, Cristina Contreras, Dolores Prieto, M. Carmen Martinez, Frédéric Gagnadoux, Ramaroson Andriantsitohaina
European Respiratory Journal 2011 38: p3469; DOI:
Simon Tual-Chalot
1INSERM U694, Université d'Angers, Angers, France
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Keita Fatoumata
1INSERM U694, Université d'Angers, Angers, France
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Pascaline Priou
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Wojciech Trzepizur
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Cristina Contreras
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Dolores Prieto
3Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain
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M. Carmen Martinez
1INSERM U694, Université d'Angers, Angers, France
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Frédéric Gagnadoux
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Ramaroson Andriantsitohaina
1INSERM U694, Université d'Angers, Angers, France
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Abstract

Obstructive sleep apnea (OSA) is characterized by repetitive apnea-hypopnea cycles during sleep, which are associated with oxygen desaturation and sleep disruption. It has been shown that level of circulating microparticles (MPs), vesicles released from plasma membrane during cell activation and apoptosis, is altered in OSA patients and contribute to endothelial dysfunction. However, their participation to reactivity in response to vasoconstrictor agonists has not yet been assessed. Two age-matched groups of patients undergoing polysomnography for OSA were compared: 15 patients with an apnea-hypopnea index (AHI)≥5 events/h were included in the OSA group and 17 control subjects with an AHI<5. MPs obtained from blood either from OSA patients or control subjects, or a vehicle were injected iv to mice. Injection of MPs from OSA patients induced vascular hyper-reactivity in response to serotonin in aorta. Interestingly, hyperreactivity was not affected by inhibition of nitric oxide (NO)-synthase (NOS) compared to control subjects and was associated with downregulation of endothelial NOS (eNOS) and decreased NO production. The non selective cyclooxygenase (COX) inhibitor or the selective COX-2 inhibitor reduced serotonin-induced hyperreactivity in aorta from OSA MP-treated mice. This effect was associated with increased COX-2 and NF-κB expressions. These data provide evidence that circulating MPs from OSA patients induce ex vivo vascular hyperreactivity by a combination of an upregulation of proinflammatory proteins and a reduced eNOS activity and NO production. These results highlight vascular dysfunction induced by MPs that might participate to events associated in OSA.

  • © 2011 ERS
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Microparticles from OSA patients induce hyper-reactivity through up-regulation of pro-inflammatory proteins
Simon Tual-Chalot, Keita Fatoumata, Pascaline Priou, Wojciech Trzepizur, Cristina Contreras, Dolores Prieto, M. Carmen Martinez, Frédéric Gagnadoux, Ramaroson Andriantsitohaina
European Respiratory Journal Sep 2011, 38 (Suppl 55) p3469;

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Microparticles from OSA patients induce hyper-reactivity through up-regulation of pro-inflammatory proteins
Simon Tual-Chalot, Keita Fatoumata, Pascaline Priou, Wojciech Trzepizur, Cristina Contreras, Dolores Prieto, M. Carmen Martinez, Frédéric Gagnadoux, Ramaroson Andriantsitohaina
European Respiratory Journal Sep 2011, 38 (Suppl 55) p3469;
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