Rabbit plaque models closely resembling lesions in human coronary artery disease

Abstract Background A suitable animal model is required to investigate plaque biology. Here, we examined 6 rabbit models of plaque generated by balloon injury and sequential combinations of normal and high-cholesterol diets. Methods and results Fifty-eight male Japanese White rabbits were used. Lipid-rich macrophages accumulated in the center of the intima, and smooth muscle cells were located on the luminal side of the intima (similar to stable plaques in human coronary arteries) of a model in which balloon injury was followed by a normal diet for 4weeks and then by a high-cholesterol diet for 4weeks. Extending the high-cholesterol diet for a further 4weeks increased accumulation of lipid-rich macrophages, diminished the amounts of elastic fibers and smooth muscle cells in the intima and caused the expression of matrix metalloproteinase-9 and tissue factor. All of these features are characteristic of unstable plaques. Moreover, quantitative analysis revealed that matrix metalloproteinase-9 expression and elastic-fiber content inversely correlated with statistical significance ( R 2 =0.52, p =0.0003). Conclusion A high-cholesterol diet for 0 to 8weeks after a normal diet for the first 4weeks following balloon injury induced various arterial lesions resembling the diffuse intimal thickening, as well as stable and unstable plaques that accumulate in human coronary arteries. The present models might be useful for plaque studies.