Comparative morphometric and immunohistological assessment of the development of restenosis after arterial injury and a cholesterol-rich diet in apolipoprotein E ???/???mice and C57BL/6 control mice

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Abstract
Animal models of restenosis have been a cornerstone of testing potential therapies and have improved the understanding of the underlying mechanisms. The aim of this study was to provide an in-depth comparison of the progression of restenotic lesion formation after arterial injury in apolipoprotein E -/- and C57BL/6 control mice. In this study, we investigated the difference in lesion formation of apolipoprotein E -/- and C57BL/6 controls on a high-cholesterol, high-fat diet after arterial injury. One week prior to arterial injury of the left femoral artery, mice were started on a high-cholesterol, high-fat diet. Diets were continued after arterial injury until euthanization. At five consecutive time points (2, 5, 10, 15, and 21 days), the intimal hyperplasia in the injured arteries was analyzed. In the C57BL/6 control mice, a continuously increasing lesion formation, consisting primarily of alpha-smooth muscle actin-positive cells, was observed. Lesion formation in apolipoprotein E -/- mice was significantly more pronounced, resulting in complete occlusion of the arteries in four out of five vessels after 21 days. Lesions in apolipoprotein E -/- mice consisted predominantly of lipid-loaded foam cells and alpha-smooth muscle actin-positive cells. Further histological evaluation demonstrated cholesterol crystals in the lesions and neovascularizsation in cases of occlusion. Thus, apoE -/- mice on a high-cholesterol, high-fat diet provide a more valid model for the characterization of the development of restenotic lesions after mechanical irritation such as angioplasty than C57BL/6 mice.