Fenofibrate increases homocystinemia through a PPARalpha-mediated mechanism.

Abstract:

:Plasma homocysteine levels increase in humans treated with fibrates but the molecular mechanisms are unknown. The goal of the present study was to determine the mechanism of this increase using animal models. Firstly, an increase in homocysteine was observed in mice treated with fenofibrate irrespective of the genetic background C57BL/6 or SV129. Secondly, as the effect of fenofibrate on gene expression is mediated through activation of the peroxisome proliferator-activated receptor alpha (PPARalpha), a transcription factor belonging to the nuclear receptor family, it was determined whether the effect of fenofibrate on homocysteine levels were modulated through PPARalpha activation. Using PPARalpha-deficient mice, it was shown that the homocysteine increase after fenofibrate treatment was completely abolished in these animals. It can be concluded that fibrates increase homocystinemia through a PPARalpha-mediated mechanism and that mice constitute an animal model for analyzing the molecular mechanisms behind the homocysteine increase after fibrate therapy in dyslipidemic patients.

journal_name

J Cardiovasc Pharmacol

authors

Luc G,Jacob N,Bouly M,Fruchart JC,Staels B,Giral P

doi

10.1097/00005344-200403000-00017

subject

Has Abstract

pub_date

2004-03-01 00:00:00

pages

452-3

issue

3

eissn

0160-2446

issn

1533-4023

pii

00005344-200403000-00017

journal_volume

43

pub_type

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