Peroxisome Proliferator-Activated Receptor-Gamma Agonists Increase Vascular Endothelial Growth Factor Expression in Human Vascular Smooth Muscle Cells

Biochem Biophys Res Commun. 2000 May 19;271(3):571-4. doi: 10.1006/bbrc.2000.2665.

Abstract

Vascular endothelial growth factor (VEGF), expressed in a variety of mesenchymal cells including vascular smooth muscle cells (VSMC), is a potent mitogen for endothelial cells, and is used clinically applied for ischemic disease of peripheral vessels. To determine whether peroxisome proliferator-activated receptor gamma (PPARgamma) regulates VEGF production in VSMC, we examined VEGF secretion from VSMC treated with PPAR agonists. Troglitazone increased VEGF secretion in a time- and dose-dependent manner (261 +/- 35% with 25 mM of troglitazone for 24 h), and also increased levels of VEGF mRNA. VEGF secretion was also increased by other PPARgamma agonists, pioglitazone, LY171883, and 15d-PGJ2 (224 +/- 17.1%, 247 +/- 36.8% and 171 +/- 7.8%, respectively), but not the PPARgamma agonists bezafibrate and Wy14643 (85.2 +/- 1.5%, 94.6 +/- 3.2, respectively). Our findings suggest that thiazolidinediones might be useful for the therapeutic angiogenesis for ischemic artery disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetophenones / pharmacology
  • Cells, Cultured
  • Chromans / pharmacology*
  • Endothelial Growth Factors / metabolism*
  • Gene Expression Regulation / drug effects
  • Humans
  • Lymphokines / metabolism*
  • Muscle, Smooth, Vascular / drug effects*
  • Peroxisome Proliferators / pharmacology*
  • Pioglitazone
  • RNA, Messenger / metabolism
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Tetrazoles / pharmacology
  • Thiazoles / pharmacology*
  • Thiazoles / therapeutic use
  • Thiazolidinediones*
  • Time Factors
  • Transcription Factors / agonists*
  • Troglitazone
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Vasodilator Agents / pharmacology

Substances

  • Acetophenones
  • Chromans
  • Endothelial Growth Factors
  • Lymphokines
  • Peroxisome Proliferators
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Tetrazoles
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Vasodilator Agents
  • LY 171883
  • Troglitazone
  • Pioglitazone