Thiazolidinediones down-regulate plasminogen activator inhibitor type 1 expression in human vascular endothelial cells: A possible role for PPAR gamma in endothelial function

The effect of peroxisome proliferator-activated receptor (PPAR) gamma activ ators, thiazolidinediones, on plasminogen activator type 1 (PAI-1) was exam ined in cultured human umbilical vein endothelial cells (HUVEC), Tumor necr osis factor alpha (TNF-alpha) enhanced PAI-1 secretion and mRNA expression by approximately 2-fold. The thiazolidinediones, troglitazone and pioglitaz one, decreased basal and TNF-alpha-stimulated PAI-1 secretion and mRNA expr ession in HUVEC in a dose-dependent fashion. PPAR gamma mRNA in HUVEC could be detected by reverse transcriptase-polymerase chain reaction using speci fic primers. These results suggest that PPAR gamma may regulate PAI-1 expre ssion in HUVEC and that thiazolidinediones have a therapeutic potential for improving endothelial dysfunction observed in insulin resistance. (C) 1999 Academic Press.