Endothelial dysfunction caused by circulating microparticles from patients with metabolic syndrome.
Microparticles are membrane vesicles that are released during cell activation and apoptosis. Elevated levels of microparticles occur in many cardiovascular diseases; therefore, we characterized circulating microparticles from both metabolic syndrome (MS) patients and healthy patients. We evaluated microparticle effects on endothelial function; however, links between circulating microparticles and endothelial dysfunction have not yet been demonstrated. Circulating microparticles and their cellular origins were examined by flow cytometry of blood samples from patients and healthy subjects. Microparticles were used either to treat human endothelial cells in vitro or to assess endothelium function in mice after intravenous injection. MS patients had increased circulating levels of microparticles compared with healthy patients, including microparticles from platelet, endothelial, erythrocyte, and procoagulant origins. In vitro treatment of endothelial cells with microparticles from MS patients reduced both nitric oxide (NO) and superoxide anion production, resulting in protein tyrosine nitration. These effects were associated with enhanced phosphorylation of endothelial NO synthase at the site of inhibition. The reduction of O2(-) was linked to both reduced expression of p47 phox of NADPH oxidase and overexpression of extracellular superoxide dismutase. The decrease in NO production was triggered by nonplatelet-derived microparticles. In vivo injection of MS microparticles into mice impaired endothelium-dependent relaxation and decreased endothelial NO synthase expression. These data provide evidence that circulating microparticles from MS patients influence endothelial dysfunction.
Agouni
Abdelali
A
INSERM U771, Centre National de la Recherche Scientifique Unité Mixte de Recherche, 6214, the Université d'Angers, Angers, France.
Lagrue-Lak-Hal
Anne Hélène
AH
Ducluzeau
Pierre Henri
PH
Mostefai
Hadj Ahmed
HA
Draunet-Busson
Catherine
C
Leftheriotis
Georges
G
Heymes
Christophe
C
Martinez
Maria Carmen
MC
Andriantsitohaina
Ramaroson
R
D000818:Animals; D001011:Aorta / Q000503:physiopathology; D001792:Blood Platelets / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000201:enzymology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology / Q000503:physiopathology*; D005260:Female; D005786:Gene Expression Regulation; D006262:Health; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000201:enzymology / Q000503:physiopathology*; D051379:Mice; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D022161:Transport Vesicles / Q000378:metabolism*; D014664:Vasodilation
D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D013481:Superoxides; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
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