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Microparticles from apoptotic monocytes enhance nitrosative stress in human endothelial cells.

Mastronardi, ML, Mostefai, HA, Soleti, R, Agouni, A, Martínez, MC and Andriantsitohaina, R (2011) Microparticles from apoptotic monocytes enhance nitrosative stress in human endothelial cells. Fundam Clin Pharmacol, 25 (6). 653 - 660. ISSN 0767-3981

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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 signaling 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 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-3-kinase 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-3-kinase pathway. In summary, monocyte microparticles active multiple pathways related to nitrosative stress in endothelial cells including both PI-3-kinase 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.

Item Type: Article
Additional Information: © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique The definitive version is available at http://onlinelibrary.wiley.com.
Divisions: Faculty of Health and Medical Sciences > Biochemistry and Physiology
Depositing User: Symplectic Elements
Date Deposited: 23 Nov 2012 10:59
Last Modified: 23 Sep 2013 19:04
URI: http://epubs.surrey.ac.uk/id/eprint/158047

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