Microparticles from apoptotic monocytes enhance nitrosative stress in human endothelial cells

Maria Letizia Mastronardi, Hadj Ahmed Mostefai, Raffaela Soleti, Abdelali Agouni, Maria Carmen Martinez, Ramaroson Andriantsitohaina

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28 Citations (Scopus)

Abstract

Microparticles are membrane vesicles with procoagulant and proinflammatory properties released during cell activation or apoptosis. Microparticles from monocytes have been implicated in atherosclerosis and vascular inflammation, but their direct effects on endothelial cells are not completely elucidated. The present study was designed to dissect the signalling pathways of monocytic microparticles in endothelial cells with respect to both NO pathway and reactive oxygen species. Microparticles were produced by treatment of human monocytic cell line THP-1 with the apoptotic agent VP-16. Human endothelial cells were treated with monocytic microparticles and then, we studied their effects on nitrosative and oxidative stresses. Incubation of human endothelial cells with microparticles enhanced the production of NO without affecting superoxide anions (O2-) generation. Microparticles did not affect endothelial NO synthase expression and its phosphorylation. Interestingly, microparticles decreased caveolin-1 expression and increased its phosphorylation. Inhibition of PI-3kinase or MEK1/2 reversed the effects of microparticles on caveolin-1 expression but not its phosphorylation. Moreover, microparticles increased nitration of several proteins, reflecting peroxynitrite production, which was prevented by blockade of PI-3kinase pathway. In summary, monocyte microparticles active multiple pathways related to nitrosative stress in endothelial cells including both PI-3kinase and ERK1/2 in the regulation of caveolin-1 expression. These data underscore the pleiotropic effect of microparticles on endothelial cells and suggest that they probably play a critical role on vascular function.
Original languageEnglish
Pages (from-to)653-660
Number of pages8
JournalFundamental & Clinical Pharmacology
Volume25
Issue number6
Early online date24 Nov 2010
DOIs
Publication statusPublished - Dec 2011

Keywords

  • endothelial cells
  • microvesicles
  • nitric oxide
  • nitrosative stress

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    Mastronardi, M. L., Mostefai, H. A., Soleti, R., Agouni, A., Martinez, M. C., & Andriantsitohaina, R. (2011). Microparticles from apoptotic monocytes enhance nitrosative stress in human endothelial cells. Fundamental & Clinical Pharmacology, 25(6), 653-660. https://doi.org/10.1111/j.1472-8206.2010.00898.x