(-)-Epigallocatechin Gallate Inhibits TNF-α-Induced PAI-1 Production in Vascular Endothelial Cells

(-)-Epigallocatechin gallate (EGCG), the major catechin derived from green tea, reduces the incidence of cardiovascular diseases such as atherosclerosis. Plasminogen activator inhibitor-1 (PAI-1) accelerates thrombus formation upon ruptured atherosclerotic plaques. However, it is not known whether or not EGCG inhibits PAI-1 production induced by tumor necrosis factor- (TNF-) in endothelial cells. This study tested the hypothesis that EGCG might have an inhibitory effect on PAI-1 production induced by TNF-. Human umbilical vein endothelial cells were cultured and incubated with TNF- and/or EGCG. The expression of p-extracellular regulated protein kinases (p-ERK1/2) and tumor necrosis factor receptor (TNFR1) protein was quantified by Western blotting, and PAI-1 levels were measured by enzyme-linked immunosorbent assay. The results showed that TNF- increased PAI-1 production in both a dose-dependent and time-dependent manner, and EGCG prevented TNF--mediated PAI-1 production and reduced phosphorylation of ERK1/2. The ERK1/2 inhibitor, PD98059 (20 mol/L), downregulated TNF--induced PAI-1 expression 57.69 +/- 2.46% (P < 0.01), but had no effect in cells pretreated with EGCG. TNF- stimulation resulted in a significant decrease in TNFR1, an effect that was abolished by pretreatment with EGCG. These results suggest that EGCG could provide vascular benefits in inflammatory cardiovascular diseases such as decreased thrombus formation associated with ruptured atherosclerotic plaques.