PPAR gamma ligands, rosiglitazone and pioglitazone, inhibit bFGF- and VEGF-mediated angiogenesis

Angiogenesis. 2008;11(4):361-7. doi: 10.1007/s10456-008-9118-0. Epub 2008 Sep 23.

Abstract

Objective: To study the effect of peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonists, pioglitazone and rosiglitazone, on vascular endothelial growth factor (VEGF)- and basic fibroblast growth factor (bFGF)-induced angiogenesis and on endothelial cell migration.

Methods: Chick chorioallantoic membrane (CAM) model was used to evaluate the efficacy of pioglitazone and rosiglitazone on VEGF- and bFGF-induced angiogenesis. In addition, the effect of pioglitazone and rosiglitazone on endothelial cell migration was evaluated using 8 mm pore filter to a feeder layer containing vitronectin as chemoattractant.

Results: Pioglitazone and rosiglitazone inhibited the pro-angiogenic effects of bFGF and VEGF in the CAM model significantly (P < 0.001) to the same extent. Endothelial cell migration was also inhibited by both pioglitazone and rosiglitazone (P < 0.001).

Conclusions: These results suggest that PPAR gamma ligands, pioglitazone and rosiglitazone, in addition to their important regulatory role in adipogenesis and inflammation, possess anti-angiogenic properties. Thus, PPAR gamma ligands may be useful in the treatment of diabetic retinopathy, macular degeneration, and other ocular disorders and may lower the risk to develop cancer in diabetic patients.

MeSH terms

  • Animals
  • Cells, Cultured
  • Chemotaxis / drug effects
  • Chick Embryo
  • Chorioallantoic Membrane / blood supply
  • Chorioallantoic Membrane / cytology
  • Chorioallantoic Membrane / drug effects
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Fibroblast Growth Factor 2 / pharmacology*
  • Humans
  • Models, Biological
  • Neovascularization, Physiologic / drug effects*
  • PPAR gamma / metabolism*
  • Pioglitazone
  • Rosiglitazone
  • Thiazolidinediones / pharmacology*
  • Vascular Endothelial Growth Factor A / pharmacology*

Substances

  • PPAR gamma
  • Thiazolidinediones
  • Vascular Endothelial Growth Factor A
  • Rosiglitazone
  • Fibroblast Growth Factor 2
  • Pioglitazone