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Etoposide treatment suppresses atherosclerotic plaque development in cholesterol-fed rabbits
M de la Llera-Moya1, G H Rothblat, J M Glick
1Department of Physiology and Biochemistry, Medical College of Pennsylvania, Philadelphia 19129.
Abstract:
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.
Insights
Etoposide treatment reduced atherosclerotic lesion development in cholesterol-fed rabbits. This drug decreased fatty streak formation and plaque thickness, potentially by inhibiting cell proliferation.
Area of Science:
- Cardiovascular Biology
- Pharmacology
- Cell Biology
Background:
- Monocytes/macrophages and smooth muscle cells are key players in atherosclerotic plaque formation.
- Atherosclerosis is a complex disease involving lipid accumulation and inflammatory responses within the arterial wall.
Purpose of the Study:
- To investigate the role of etoposide in modulating atherosclerotic plaque development.
- To explore the cellular mechanisms underlying etoposide's effects on atherosclerosis.
Main Methods:
- New Zealand White rabbits were fed a high-cholesterol diet and treated with etoposide.
- Aortic intima was examined for atherosclerotic lesion extent and composition.
- Blood cell counts and lipid levels were monitored.
Main Results:
- Long-term etoposide treatment significantly reduced fatty streak formation in the aortic intima.
- Etoposide-treated rabbits exhibited thinner plaques with reduced fibrous tissue and fewer smooth muscle cell-derived foam cells.
- These effects were independent of hyperlipemia or changes in blood cell counts.
Conclusions:
- Etoposide inhibits the development of diet-induced atherosclerosis in rabbits.
- The drug's anti-atherosclerotic effects may be mediated by the inhibition of intimal cell proliferation.
- Etoposide represents a potential therapeutic agent for managing atherosclerosis.