Cadmium injures tube formation by cultured human vascular endothelial cells

The effect of cadmium chloride (Cd; CdCl2) on the tube formation by cultured human umbilical vascular endothelial cells (HUVEC) was examined. HUVEC were collected by enzymatic digestion with collagenase. Tube formation was studied by culturing the cells on a gelled basement membrane matrix (Matrigel). Treatment of HUVEC with 0.1 microM-1.0 mM Cd for 24 hours inhibited tube formation dose-dependently. The cadmium concentration inhibiting tube formation by 50% relative to untreated cells was about 150 microM. The length of tube formation decreased time-dependently with 150 microM Cd. The treatment of HUVEC by 50 nM of beta-phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, increased tube formation. However, the inhibitory effect of Cd on tube formation was not affected by the addition of PMA. The pretreatment of the Matrigel by Cd inhibited tube formation similarly to the results of Cd treatment. These findings suggest that Cd inhibits the formation of a capillary network by HUVEC, and that the Cd-inhibitory effect on tube formation may have been dependent in this study on the degeneration of Matrigel by Cd.