Cellular and Molecular Life Sciences CMLS

, Volume 60, Issue 4, pp 810–819

Fenofibrate inhibits angiogenesis in vitro and in vivo

  • J. Varet
  • L. Vincent
  • P. Mirshahi
  • J.-V. Pille
  • E. Legrand
  • P. Opolon
  • Z. Mishal
  • J. Soria
  • H. Li
  • C. Soria
Research Article

DOI: 10.1007/s00018-003-2322-6

Cite this article as:
Varet, J., Vincent, L., Mirshahi, P. et al. CMLS, Cell. Mol. Life Sci. (2003) 60: 810. doi:10.1007/s00018-003-2322-6

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.

Copyright information

© Birkhäuser Verlag, 2003

Authors and Affiliations

  • J. Varet
    • 1
  • L. Vincent
    • 1
  • P. Mirshahi
    • 1
  • J.-V. Pille
    • 1
  • E. Legrand
    • 1
  • P. Opolon
    • 3
  • Z. Mishal
    • 4
  • J. Soria
    • 2
  • H. Li
    • 1
  • C. Soria
    • 1
  1. 1.Laboratoire 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 FR
  2. 2.Laboratoire de Biochimie et Equipe Mixte Institut National de la Santé et de la Recherche Médicale (INSERM) 99-12, Hôtel-Dieu, 75 Paris (France)FR
  3. 3.Institut Gustave Roussy, 95 Villejuif (France)FR
  4. 4.Centre National de Recherche Scientifique (CNRS), IFR 2249, Villejuif (France)FR
  5. 5.INSERM Unité 553, Hôpital Saint Louis, 75 Paris (France)FR