ETOPOSIDE TREATMENT SUPPRESSES ATHEROSCLEROTIC PLAQUE DEVELOPMENT IN CHOLESTEROL-FED RABBITS

To study the mechanisms by which monocytes/macrophages and smooth muscle cells contribute to atherosclerotic lesions, we studied atherosclerotic plaque formation in cholesterol-fed rabbits treated with etoposide, a drug that has been shown to have several effects that could interfere with the proposed interactions between these two cell types (M.W. Aarnoudes et al, Virchows Arch B 1984;47:211-216 and M. Rozencweig et al, Cancer 1977;40:334-342). Our results show that long-term etoposide treatment of New Zealand White rabbits maintained on a high-cholesterol diet decreases the extent of fatty streak formation in the aortic intima. Moreover, the plaques formed in the presence of etoposide are thinner and at least focally have less fibrous tissue and fewer smooth muscle cell-derived foam cells than do plaques in control rabbits. These effects are independent of the extent of the diet-induced hyperlipemia or an effect of etoposide on blood cell count and may be related to the inhibition of intimal cell proliferation by etoposide.