Induction of Plasminogen Activator Inhibitor Type 1 Synthesis by Cadmium in Human Vascular Endothelial Cells in Culture.

Abstract

Cadmium is a unique heavy metal that stimulates the secretion of plasminogen activator inhibitor type 1 (PAI-1) from vascular endothelial cells. However, it has been incompletely understood whether cadmium stimulation of PAI-1 secretion actually results in a reduction of endothelial fibrinolytic activity and whether the stimulation results from an induction of endothelial PAI-1 synthesis. To address these questions, human umbilical vein endothelial cells were cultured with cadmium chloride in the presence or absence of actinomycin D, H-7 or HA1004. The activity of tissue type and urokinase type plasminogen activators (t-PA and u-PA, respectively) in the conditioned medium was analyzed by fibrin zymography and mRNAs coding t-PA, u-PA and PAI-1 were determined by quantitative reverse transcription-polymerase chain reaction. Results of the experiments indicate that cadmium reduces the activity of both t-PA and u-PA in vascular endothelial cells through induction of PAI-1 synthesis which is mediated by protein kinase C activation. Since the PAI-1 induction by cadmium was observed in neither human vascular smooth muscle cells nor human fibroblasts, it was suggested that vascular endothelial cells are a particular cell type of which PAI-1 synthesis is stimulated by cadmium.