Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, prevents microparticle-induced vascular hyporeactivity through the regulation of proinflammatory proteins.
Microparticles are plasma membrane vesicles with procoagulant and proinflammatory properties. We recently demonstrated that microparticles induce vascular hyporeactivity and evoke up-regulation of proinflammatory protein expression. This study dissected the effect of either in vitro treatment or short-term oral administration of the peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist, rosiglitazone, on microparticle-induced vascular hyporeactivity of mouse vessels. Microparticles were produced from T cells by actinomycin D treatment. The effects of rosiglitazone on mouse aortic rings incubated with microparticles were investigated. Aortae treated in vitro with rosiglitazone or aortae taken from mice treated by oral administration of the same agonist completely prevented microparticle-induced vascular hyporeactivity in response to U46619 [9,11-dideoxy-11alpha, 9alpha-epoxymethanoprostaglandin F(2alpha)). These effects of rosiglitazone occurred independently of the presence of endothelium without modifications in blood parameters. The mechanisms involved abrogation of nitric oxide (NO) and prostacyclin overproduction linked to up-regulation of inducible NO-synthase and cyclooxygenase 2 elicited by microparticles. In addition, rosiglitazone treatment reduced the ability of microparticles to evoke increases in interleukin (IL)-6, IL-8, and nuclear factor (NF)-kappaB transcription, and NF-kappaB expression and activation. These results suggest that rosiglitazone, via PPARgamma activation, counteracts vascular dysfunction associated with increased release of proinflammatory proteins elicited by microparticles. They underscore therapeutic perspective for rosiglitazone in vascular diseases involving enhanced participation of microparticles.
Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 771-Centre National de la Recherche Scientifique Unité Mixte de Recherche 6214, Faculté de Médecine, rue Haute de Reculée, 49045 Angers, France.
Angela
A
Tesse
Ghassan
G
Al-Massarani
Rosemary
R
Wangensteen
Sebastien
S
Reitenbach
M Carmen
MC
Martínez
Ramaroson
R
Andriantsitohaina
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D022162:Cytoplasmic Vesicles / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D014657:Vasculitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*
D008565:Membrane Proteins; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone