Effects of cadmium on the release of tissue plasminogen activator and plasminogen activator inhibitor type 1 from cultured human vascular smooth muscle cells and fibroblasts

Abstract

To evaluate the toxicity of cadmium on the blood fibrinolytic system during hemostasis, human vascular smooth muscle cells and human fibroblasts were cultured in the presence of cadmium chloride. It was found that cadmium markedly decreased the release of both tissue plasminogen activator antigen (t-PA:Ag) and plasminogen activator inhibitor type-1 antigen (PAI-l:Ag) from vascular smooth muscle cells. Other heavy metals including lead, manganese, mercury and nickel also decreased the t-PA:Ag and PAI-l:Ag release, however, cadmium was the most potent inhibitor. On the other hand, the release of t-PA:Ag was significantly increased whereas that of PAI-l:Ag was unaffected in fibroblasts after exposure to cadmium. Of the tested heavy metals, only cadmium increased the t-PA:Ag release from the cells. Electrophoretic enzymography revealed that cadmium reduced the activity of plasminogen activators in the conditioned medium of both vascular smooth muscle cells and fibroblasts. Cadmium markedly decreased the incorporation of [ 3H]leucine accompanied with a significant increase in the leakage of lactate dehydrogenase in vascular smooth muscle cells; however, the metal did not change these markers in fibroblasts. These results suggest that the regulation of fibrinolysis mediated by vascular smooth muscle cells and fibroblasts during hemostasis may be disturbed by cadmium.