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Microparticles from patients with metabolic syndrome induce vascular hypo-reactivity via Fas/Fas-Ligand pathway in mice

Agouni, A, Ducluzeau, PH, Benameur, T, Faure, S, Sladkova, M, Duluc, L, Leftheriotis, G, Pechanova, O, Delibegovic, M and Martinez, MC (2011) Microparticles from patients with metabolic syndrome induce vascular hypo-reactivity via Fas/Fas-Ligand pathway in mice PloS ONE, 6 (11), e27809.

Microparticles from Patients with Metabolic Syndrome Induce Vascular Hypo-Reactivity.pdf - Version of Record

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Microparticles are membrane vesicles with pro-inflammatory properties. Circulating levels of microparticles have previously been found to be elevated in patients with metabolic syndrome (MetS). The present study aimed to evaluate the effects of in vivo treatment with microparticles, from patients with MetS and from healthy subjects (HS), on ex vivo vascular function in mice. Microparticles isolated from MetS patients or HS, or a vehicle were intravenously injected into mice, following which vascular reactivity in response to vasoconstrictor agonists was assessed by myography with respect to cyclo-oxygenase pathway, oxidative and nitrosative stress. Injection of microparticles from MetS patients into mice induced vascular hyporeactivity in response to serotonin. Hypo-reactivity was associated with up-regulation of inducible NO-synthase and increased production of NO, and was reversed by the NOsynthase inhibitor (NG-nitro-L-arginine). The selective COX-2 inhibitor (NS398) reduced the contractile effect of serotonin in aortas from mice treated with vehicle or HS microparticles; however, this was not observed within mice treated with MetS microparticles, probably due to the ability of MetS microparticles to enhance prostacyclin. MetS microparticle-mediated vascular dysfunction was associated with increased reactive oxygen species (ROS) and enhanced expression of the NADPH oxidase subunits. Neutralization of the pro-inflammatory pathway Fas/FasL completely prevented vascular hypo-reactivity and the ability of MetS microparticles to enhance both inducible NO-synthase and monocyte chemoattractant protein-1 (MCP-1). Our data provide evidence that microparticles from MetS patients induce ex vivo vascular dysfunction by increasing both ROS and NO release and by altering cyclooxygenase metabolites and MCP-1 through the Fas/FasL pathway.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Biochemical Sciences
Authors :
Agouni, A
Ducluzeau, PH
Benameur, T
Faure, S
Sladkova, M
Duluc, L
Leftheriotis, G
Pechanova, O
Delibegovic, M
Martinez, MC
Date : 15 November 2011
DOI : 10.1371/journal.pone.0027809
Contributors :
ContributionNameEmailORCID, PH
Related URLs :
Additional Information : © 2011 Agouni et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Depositing User : Symplectic Elements
Date Deposited : 25 Jan 2012 08:48
Last Modified : 31 Oct 2017 14:21

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