Research Article

Cellular and Molecular Life Sciences CMLS

, Volume 60, Issue 4, pp 810-819

First online:

Fenofibrate inhibits angiogenesis in vitro and in vivo

  • J. VaretAffiliated withLaboratoire DIFEMA, Faculté de Médecine et Pharmacie, 22 Boulevard Gambetta, 76183 Rouen (France), Fax +33 2 35 14 83 40, e-mail: claudine.soria@lrb.ap-hop-paris.fr
  • , L. VincentAffiliated withLaboratoire DIFEMA, Faculté de Médecine et Pharmacie, 22 Boulevard Gambetta, 76183 Rouen (France), Fax +33 2 35 14 83 40, e-mail: claudine.soria@lrb.ap-hop-paris.fr
  • , P. MirshahiAffiliated withLaboratoire DIFEMA, Faculté de Médecine et Pharmacie, 22 Boulevard Gambetta, 76183 Rouen (France), Fax +33 2 35 14 83 40, e-mail: claudine.soria@lrb.ap-hop-paris.fr
  • , J.-V. PilleAffiliated withLaboratoire DIFEMA, Faculté de Médecine et Pharmacie, 22 Boulevard Gambetta, 76183 Rouen (France), Fax +33 2 35 14 83 40, e-mail: claudine.soria@lrb.ap-hop-paris.fr
  • , E. LegrandAffiliated withLaboratoire DIFEMA, Faculté de Médecine et Pharmacie, 22 Boulevard Gambetta, 76183 Rouen (France), Fax +33 2 35 14 83 40, e-mail: claudine.soria@lrb.ap-hop-paris.fr
  • , P. OpolonAffiliated withInstitut Gustave Roussy, 95 Villejuif (France)
  • , Z. MishalAffiliated withCentre National de Recherche Scientifique (CNRS), IFR 2249, Villejuif (France)
  • , J. SoriaAffiliated withLaboratoire de Biochimie et Equipe Mixte Institut National de la Santé et de la Recherche Médicale (INSERM) 99-12, Hôtel-Dieu, 75 Paris (France)
  • , H. LiAffiliated withLaboratoire DIFEMA, Faculté de Médecine et Pharmacie, 22 Boulevard Gambetta, 76183 Rouen (France), Fax +33 2 35 14 83 40, e-mail: claudine.soria@lrb.ap-hop-paris.fr
    • , C. SoriaAffiliated withLaboratoire DIFEMA, Faculté de Médecine et Pharmacie, 22 Boulevard Gambetta, 76183 Rouen (France), Fax +33 2 35 14 83 40, e-mail: claudine.soria@lrb.ap-hop-paris.fr

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Abstract.

Fenofibrate, a peroxisome proliferator-activated receptor (PPAR)-alpha activator, used as a normolipidemic agent, is thought to offer additional beneficial effects in atherosclerosis. Since angiogenesis is involved in plaque progression, hemorrhage, and instability, the main causes of ischemic events, this study was designed to evaluate the action of fenofibrate on angiogenesis. Our results show that fenofibrate (i) inhibits endothelial cell proliferation induced by angiogenic factors, followed at high concentrations by an increase in apoptosis, (ii) inhibits endothelial cell migration in a healing wound model, (iii) inhibits capillary tube formation in vitro, and (iv) inhibits angiogenesis in vivo. Concerning the mechanism of action, the inhibition of endothelial cell migration by fenofibrate can be explained by a disorganization of the actin cytoskeleton. At the molecular level, fenofibrate markedly decreased basic fibroblast growth factor-induced Akt activation and cyclooxygenase 2 gene expression. This inhibition of angiogenesis could participate in the beneficial effect of fenofibrate in atherosclerosis.

Key words. Angiogenesis; atherosclerosis; fenofibrate; Akt; cyclooxygenase 2; peroxisome proliferator activated receptor.