Endothelial dysfunction caused by circulating microparticles from patients with metabolic syndrome

Abdelali Agouni, Anne Hélène Lagrue-Lak-Hal, Pierre Henri Ducluzeau, Hadj Ahmed Mostefai, Catherine Draunet-Busson, Georges Leftheriotis, Christophe Heymes, Maria Carmen Martinez, Ramaroson Andriantsitohaina

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Abstract

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.
Original languageEnglish
Pages (from-to)1210-1219
Number of pages10
JournalAmerican Journal of Pathology
Volume173
Issue number4
Early online date4 Sep 2008
DOIs
Publication statusPublished - Oct 2008

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Keywords

  • Animals
  • Aorta
  • Blood Platelets
  • Cytokines
  • Endothelial Cells
  • Endothelium, Vascular
  • Female
  • Gene Expression Regulation
  • Health
  • Humans
  • Inflammation Mediators
  • Male
  • Metabolic Syndrome X
  • Mice
  • Middle Aged
  • Nitric Oxide
  • Nitric Oxide Synthase Type III
  • RNA, Messenger
  • Superoxides
  • Transport Vesicles
  • Vasodilation

Cite this

Agouni, A., Lagrue-Lak-Hal, A. H., Ducluzeau, P. H., Mostefai, H. A., Draunet-Busson, C., Leftheriotis, G., ... Andriantsitohaina, R. (2008). Endothelial dysfunction caused by circulating microparticles from patients with metabolic syndrome. American Journal of Pathology, 173(4), 1210-1219. https://doi.org/10.2353/ajpath.2008.080228