Effects of metal ions on proliferation of aortic smooth muscle cells and myoblastic cellsin vitro

Metal ions released from implanted stents into the surrounding tissue may contribute to vascular reactions which cause restenosis in about 30%. This assumption prompted us to investigate short term effects of metal ions (Ag, Al, Cr, Fe, Mo, Ni, V, all applied as chloride salts) on proliferation of swine aortic smooth muscle cells (SMC) and a Myoblastic cell line (C2Cl2). Cell confluence was 30 or 50% when metal ions were added and cell growth was monitored with the MTT-test after 2 days. A clear concentration dependence of acute toxicity, of the different metal ions was found for both cell types. The order of toxicity indicated by IC50 values was V > Ni > Fe > Mo > Al > Cr. The nearly insoluble silverchloride exerted unclear effects, In experiments starting at high confluence, the apparent toxicity of Fe, Ni, and V,,vas reduced. Al, Which to Our knowledge is not a major constituent in medical stents, was the only metal ion found here to cause a slightly increased proliferation, but this effect was restricted to the low concentration range (16-250 mumol/l). In general, results for both cell types, C2Cl2 and SMC, were very similar. We conclude that short term effects of metal ions, which may be released in the interface of stent and vessel wall tissue, comprise a reduction rather than a stimulation of cell proliferation. However, restenosis may be initiated as a complex tissue reaction to primary toxic metal effects.