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PPARalpha agonists inhibit tissue factor expression in human monocytes and macrophages
B P Neve1, D Corseaux, G Chinetti
1Département d'Athérosclérose, U.325 INSERM, Institut Pasteur de Lille, and the Faculté de Pharmacie, Université de Lille II, France.
Circulation
|February 24, 2001
Summary
Peroxisome proliferator-activated receptor-alpha (PPARα) agonists, like fibrates, reduce tissue factor (TF) gene expression in monocytes and macrophages. This suggests PPARα activation may control atherosclerotic plaque thrombogenicity.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Thrombosis Research
Background:
- Monocytic tissue factor (TF) expression contributes to thrombogenicity in vascular lesions.
- Endotoxin induces TF expression via AP-1 and NF-kappaB, pathways modulated by peroxisome proliferator-activated receptor-alpha (PPARα).
Purpose of the Study:
- To investigate the effects of fibrates and other PPARα agonists on TF expression in monocytes.
Main Methods:
- Assessed PPARα expression in THP-1 cells and primary human monocytes/macrophages.
- Measured TF mRNA and activity following stimulation with lipopolysaccharide or interleukin-1β in the presence of PPARα agonists (fenofibric acid, WY14643, GW2331).
Main Results:
- PPARα protein is expressed in THP-1 cells, similar to primary human monocytes.
- PPARα agonists significantly inhibited TF mRNA upregulation and TF activity induced by lipopolysaccharide or interleukin-1β in both cell lines and primary cells.
Conclusions:
- PPARα activation leads to downregulation of the TF gene.
- PPARα plays a novel role in controlling atherosclerotic plaque thrombogenicity by modulating TF expression in monocytes and macrophages.
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