Peroxisome proliferator-activated receptor-gamma agonists increase vascular endothelial growth factor expression in human vascular smooth muscle cells.
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.
Yamakawa
K
K
Second Department of Internal Medicine, Osaka City University Medical School, Osaka, 545-8586, Japan.
Hosoi
M
M
Koyama
H
H
Tanaka
S
S
Fukumoto
S
S
Morii
H
H
Nishizawa
Y
Y
D000098:Acetophenones / Q000494:pharmacology; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008222:Lymphokines / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D013777:Tetrazoles / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use; D045162:Thiazolidinediones; D013997:Time Factors; D014157:Transcription Factors / Q000819:agonists*; D000077288:Troglitazone; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014665:Vasodilator Agents / Q000494:pharmacology
D000098:Acetophenones; D002839:Chromans; D016228:Endothelial Growth Factors; D008222:Lymphokines; D020025:Peroxisome Proliferators; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013777:Tetrazoles; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014665:Vasodilator Agents; C044660:LY 171883; D000077288:Troglitazone; D000077205:Pioglitazone