Cadmium stimulation of plasminogen activator inhibitor-1 release from human vascular endothelial cells in culture.

We investigated the effect of cadmium (0.5, 1.0 or 2.0 microM) on the release of plasminogen activator inhibitor-1 antigen (PAI-1:Ag) from cultured human vascular endothelial cells. It was found that cadmium at 1.0 and 2.0 microM significantly increased the PAI-1:Ag release from the cells after a 24-h incubation. However, the tissue plasminogen activator antigen (t-PA:Ag) release was not changed by the metal. Although nickel as well as cadmium increased the PAI-1:Ag release, the other heavy metals including cobalt, zinc and copper did not exhibit such a stimulatory effect. The incorporation of [3H]leucine into the acid-insoluble fraction of the cell layer was unchanged by cadmium, suggesting that the metal may stimulate the synthesis of PAI-1 without association with generalized increase in protein synthesis. Cadmium at 1.0 and 2.0 microM significantly decreased the t-PA activity in the medium. The present study showed that cadmium increases the release of PAI-I:Ag from cultured endothelial cells without non-specific stimulation of protein synthesis. The decrease in the t-PA activity suggests an implication of cadmium in vascular lesion which is mediated by anti-fibrinolytic activity.