Characterization of atherosclerotic lesions in apo E3-leiden transgenic mice
Abstract
Apo E3-leiden transgenic mice express human dysfunctional apo E variant and develop hyperlipidemia and atherosclerosis on a high fat/high cholesterol diet. We characterized diet-induced atherosclerotic lesions in apo E3-leiden transgenic mice using immunocytochemical methods in order to examine foam cell formation and determine whether advanced atherosclerotic lesions develop in these animals. Special attention was given to the presence of oxidized lipoproteins and expression of lipoprotein receptors. Plasma cholesterol levels in apo E3-leiden mice on an atherogenic diet increased from 2 to 36 mmol/l in 4 months. At this time apo E3-leiden mice had developed lesions, which ranged from early fatty streaks in thoracic and abdominal aorta to advanced lesions in aortic arch. Early fatty streaks were entirely composed of macrophages which also expressed scavenger receptors. Epitopes characteristic of oxidized LDL were present in macrophage-rich foam cells. Advanced atherosclerotic lesions also developed in apo E3-leiden mice including smooth muscle cell cap formation and erosion of the media. Macrophages and epitopes characteristic of oxidized LDL were present in core and shoulder regions. Scavenger receptors were expressed in macro...Continue Reading
References
Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis
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