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01-09-2005 | Experimental

Pretreatment with peroxysome proliferator-activated receptor α agonist fenofibrate protects endothelium in rabbit Escherichia coli endotoxin-induced shock

Authors: Eric Wiel, Gilles Lebuffe, Emmanuel Robin, Gaëlle Gasan, Delphine Corseaux, Benoît Tavernier, Brigitte Jude, Régis Bordet, Benoît Vallet

Published in: Intensive Care Medicine | Issue 9/2005

Abstract

Objective

To investigate the effects of fenofibrate, an activator of peroxysome proliferator activated receptor (PPAR) α, on vascular endothelium and on hemostasis in a rabbit endotoxic shock model.

Design and setting

Prospective laboratory study in a university laboratory.

Subjects

36 male New Zealand rabbits weighing 2.5–3 kg.

Interventions

We determined in vitro vascular reactivity, endothelium CD31–platelet/endothelial cell adhesion molecule (PECAM) 1 immunohistochemistry, plasma coagulation factors, and monocyte tissue factor expression 5 days after onset of endotoxic shock (0.5 mg/kg intravenous bolus, Escherichia coli lipopolysaccharide) with or without treatment by fenofibrate (mixed in the chow at a concentration of 0.5%) for 15 days before lipopolysaccharide injection and 5 days afterward.

Measurements and results

Metabolic acidosis and coagulation activation confirmed presence of shock. Fenofibrate decreased monocyte tissue factor expression. It improved endothelial-dependent relaxation at 5 days (Emax=68.2±3.3%, vs. 44.2±2.5% in the non-treated group). Endotoxin-induced deendothelialization was significantly decreased by fenofibrate at 5 days (8.5±1.3% vs. 19.2±3.1% in the nontreated group).

Conclusions

These data indicate for the first time that fenofibrate, an activator of PPAR-α, inhibits monocyte tissue factor expression and protects against endothelial dysfunction and histological injury in endotoxin-induced shock.

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Title: Pretreatment with peroxysome proliferator-activated receptor α agonist fenofibrate protects endothelium in rabbit Escherichia coli endotoxin-induced shock
Authors: Eric Wiel
Gilles Lebuffe
Emmanuel Robin
Gaëlle Gasan
Delphine Corseaux
Benoît Tavernier
Brigitte Jude
Régis Bordet
Benoît Vallet
Publication date: 01-09-2005
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 9/2005
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-005-2730-1

At a glance: The STEP trials

Springer Medicine

Pretreatment with peroxysome proliferator-activated receptor α agonist fenofibrate protects endothelium in rabbit Escherichia coli endotoxin-induced shock

Abstract

Objective

Design and setting

Subjects

Interventions

Measurements and results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Objective

Design and setting

Subjects

Interventions

Measurements and results

Conclusions

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