Stimulation of cultured vascular smooth muscle cell proliferation by thrombospondin is potentiated by zinc.

The interaction of zinc sulfate with thrombospondin (TSP) derived from bovine platelets, on the proliferation of bovine aortic smooth muscle cells was investigated using cell culture. Zinc alone has no effect but potentiates the stimulatory effect of TSP on the incorporation of [3H]thymidine into the acid-insoluble cell fraction. Other heavy metals including copper, lead, manganese and nickel did not exhibit a similar effect. In bovine aortic endothelial cells, [3H]thymidine incorporation was stimulated by zinc alone and suppressed by TSP alone; the stimulation by zinc was significantly reduced by TSP. In human fibroblastic IMR-90 cells, [3H]thymidine incorporation was stimulated by either zinc or TSP; a simultaneous treatment with zinc and TSP showed an additive effect. The present data suggest that zinc may be a unique heavy metal that potentiates the proliferation of vascular smooth muscle cells stimulated by TSP; in addition, such an interaction was observed selectively in this cell type. Since a large amount of TSP is released from alpha-granules of aggregated platelets, zinc may augment TSP activity which is involved in the physiology of vascular tissues.