PMID- 22110764
OWN - NLM
STAT- MEDLINE
DCOM- 20120326
LR  - 20220321
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 11
DP  - 2011
TI  - Microparticles from patients with metabolic syndrome induce vascular 
      hypo-reactivity via Fas/Fas-ligand pathway in mice.
PG  - e27809
LID - 10.1371/journal.pone.0027809 [doi]
LID - e27809
AB  - 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 hypo-reactivity 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 NO-synthase inhibitor (N(G)-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 cyclo-oxygenase metabolites and MCP-1 through the Fas/FasL pathway.
FAU - Agouni, Abdelali
AU  - Agouni A
AD  - INSERM, U694, Angers, France.
FAU - Ducluzeau, Pierre-Henri
AU  - Ducluzeau PH
FAU - Benameur, Tarek
AU  - Benameur T
FAU - Faure, Sebastien
AU  - Faure S
FAU - Sladkova, Martina
AU  - Sladkova M
FAU - Duluc, Lucie
AU  - Duluc L
FAU - Leftheriotis, Georges
AU  - Leftheriotis G
FAU - Pechanova, Olga
AU  - Pechanova O
FAU - Delibegovic, Mirela
AU  - Delibegovic M
FAU - Martinez, Maria Carmen
AU  - Martinez MC
FAU - Andriantsitohaina, Ramaroson
AU  - Andriantsitohaina R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111115
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Fas protein, mouse)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (fas Receptor)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.6.3.- (NADPH Oxidases)
SB  - IM
MH  - Animals
MH  - Aorta/*cytology/*metabolism
MH  - Cell-Derived Microparticles/*metabolism
MH  - Chemokine CCL2/genetics/metabolism
MH  - Cyclooxygenase 2/metabolism
MH  - Fas Ligand Protein/*metabolism
MH  - Female
MH  - Gene Expression Regulation, Enzymologic
MH  - Humans
MH  - Male
MH  - Metabolic Syndrome/*pathology
MH  - Mice
MH  - Middle Aged
MH  - NADPH Oxidases/metabolism
MH  - Nitric Oxide/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - *Signal Transduction
MH  - fas Receptor/*metabolism
PMC - PMC3217000
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2011/11/24 06:00
MHDA- 2012/03/27 06:00
PMCR- 2011/11/15
CRDT- 2011/11/24 06:00
PHST- 2011/07/06 00:00 [received]
PHST- 2011/10/25 00:00 [accepted]
PHST- 2011/11/24 06:00 [entrez]
PHST- 2011/11/24 06:00 [pubmed]
PHST- 2012/03/27 06:00 [medline]
PHST- 2011/11/15 00:00 [pmc-release]
AID - PONE-D-11-14895 [pii]
AID - 10.1371/journal.pone.0027809 [doi]
PST - ppublish
SO  - PLoS One. 2011;6(11):e27809. doi: 10.1371/journal.pone.0027809. Epub 2011 Nov 15.