title: Circulating microparticles from patients with obstructive sleep apnea enhance vascular contraction: mandatory role of the endothelium.
abstract: Obstructive sleep apnea (OSA) is characterized by repetitive apnea-hypopnea cycles during sleep associated with oxygen desaturation and sleep disruption. We evaluated the role of circulating microparticles (MPs) from patients with OSA in the regulation of vascular function. MPs from whole blood from patients with OSA or control subjects were injected i.v. into mice. Injection of MPs from patients with OSA induced ex vivo vascular hyperreactivity in aortas with functional endothelium but, in contrast, hyporeactivity in vessels without functional endothelium. Vascular hyperreactivity was blunted in the presence of a nitric oxide synthase inhibitor alone or combined with the cyclooxygenase inhibitor indomethacin. MPs from patients with OSA reduced endothelial nitric oxide synthase activity and nitric oxide production, increased aortic cyclooxygenase-1 and cyclooxygenase-2 expression, and increased thromboxane A(2) and prostacyclin production. Blockade of thromboxane A(2) receptor did not affect the serotonin response in arteries from OSA MP-treated mice. A superoxide dismutase mimetic reduced the vascular hyperreactivity induced by MPs from patients with OSA but had no effect on contraction in vessels from control and non-OSA MP-treated mice. These data provide evidence that circulating MPs from patients with OSA induce ex vivo vascular hyperreactivity with the obligatory role of the endothelium and subtle interactions between the nitric oxide and cyclooxygenase pathways and metabolites. These results highlight the participation of MPs in vascular dysfunction associated with OSA.
authors: L'Université Nantes, Angers, Le Mans, Angers, France.
authors: Simon
authors: S
authors: Tual-Chalot
authors: Keita
authors: K
authors: Fatoumata
authors: Pascaline
authors: P
authors: Priou
authors: Wojciech
authors: W
authors: Trzepizur
authors: Abderahim
authors: A
authors: Gaceb
authors: Cristina
authors: C
authors: Contreras
authors: Dolores
authors: D
authors: Prieto
authors: Maria Carmen
authors: MC
authors: Martinez
authors: Frédéric
authors: F
authors: Gagnadoux
authors: Ramaroson
authors: R
authors: Andriantsitohaina
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010641:Phenotype; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D020181:Sleep Apnea, Obstructive / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D055815:Young Adult
chemical_list: D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D012701:Serotonin; D052250:Nitric Oxide Synthase Type III; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D013482:Superoxide Dismutase