Pretreatment with Peroxysome Proliferator-activated Receptor Alpha Agonist Fenofibrate Protects Endothelium in Rabbit Escherichia Coli Endotoxin-induced Shock

Overview

Journal Intensive Care Med

Specialty Critical Care

Date 2005 Sep 1

PMID 16132896

Citations 13

Authors

Eric Wiel

Gilles Lebuffe

Emmanuel Robin

Gaelle Gasan

Delphine Corseaux

Benoit Tavernier

Brigitte Jude

Regis Bordet

Benoit Vallet

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate the effects of fenofibrate, an activator of peroxysome proliferator activated receptor (PPAR) alpha, 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-alpha, inhibits monocyte tissue factor expression and protects against endothelial dysfunction and histological injury in endotoxin-induced shock.

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