Stimulation by zinc of cultured vascular endothelial cell proliferation: possible involvement of endogenous basic fibroblast growth factor.

Vascular endothelial cells from bovine aorta were cultured with zinc sulfate (20 microM or less) for 24 h and labeled with [3H]thymidine or [14C]leucine during the last 3 h of the culture. It was found that the cell number was significantly increased by zinc alone; the incorporation of both [3H]thymidine and [14C]leucine was also stimulated by the metal. The stimulation by zinc occurred in the presence or absence of exogenous basic fibroblast growth factor (bFGF). However, other heavy metals including copper, manganese and nickel did not exhibit such a stimulatory effect, suggesting that zinc plays a particular role in endothelial cell proliferation. Stimulation of the [3H]thymidine incorporation by zinc disappeared in the presence of either cycloheximide or anti-bFGF IgG; in addition, a lipoxygenase inhibitor nordihydroguaiaretic acid diminished the zinc stimulation but a cyclooxygenase inhibitor indomethacin did not exhibit such an inhibitory effect. These results indicated that zinc stimulated the proliferation of endothelial cells through the lipoxygenase pathway which mediates the stimulation by endogenous bFGF. In other words, the metal may amplify the endogenous bFGF-dependent proliferation of the cells.