Peroxisome proliferator-activated receptor gamma mediated inhibition of plasminogen activator inhibitor type 1 production and proliferation of human umbilical vein endothelial cells

Abstract 

Insulin resistance and diabetes mellitus promote the atherosclerotic process, where an endothelial dysfunction plays a key role. The diabetic milieu elevates the production of the plasminogen activator inhibitor type 1 (PAI-1) and also increases the proliferation of vascular endothelial cells. Recently the role of peroxisome proliferator-activated receptor gamma (PPARγ) in atherosclerosis has been extensively studied. However, the direct effect of PPARγ in vascular endothelial cells is still unclear. Therefore, the effect of PPARγ was investigated to determine if it plays an important role in PAI-1 production and cellular proliferation in human umbilical vein endothelial cells (HUVEC). A combination of PPARγ-overexpression and troglitazone treatment (5 ug/ml) significantly decreased both the PAI-1 mRNA and protein expression, while PPARγ-overexpression or troglitazone alone tended to decrease both the PAI-1 protein and mRNA expression. PPARγ-overexpression or troglitazone treatment alone reduced the thymidine uptake by the HUVEC with or without TNFα treatment. There was a further decrease in the thymidine uptake with troglitazone treatment in the PPARγ-overexpressed HUVEC. In conclusion, PPARγ can reduce PAI-1 production in HUVEC directly by transcriptional repression, and may play a beneficial role in preventing cardiovascular events. PPARγ can also inhibit vascular endothelial cell proliferation, and its clinical relevance in diabetic vascular complications should be elucidated.

Keywords: Plasminogen activator inhibitor type 1, Peroxisome proliferator-activated receptor gamma, Troglitazone, Endothelial cell