Uptake and distribution of 3H-cholesteryl oleyl ether in tissues of cholesterol-fed New Zealand White and Watanabe Heritable Hyperlipidemic rabbits
McCormack, Cynthia J.
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Cholesterol-fed New Zealand White (CH-FED) and Watanabe Heritable Hyperlipidemic (WHHL) rabbits with minimal, moderate, and severe atherosclerosis were injected with a non-degradable cholesteryl ester analogue, 3H-cholesteryl oleyl ether (3H-COE), to identify organs and cells active in the uptake of plasma cholesteryl ester (CE) at critical stages in the progression of atherosclerosis. The iliac arteries were injured by balloon catheterization to compare the repair process between the two animals. The morphology of the atherosclerotic lesions and the physical state of the arterial lipid were also compared. The atherosclerotic lesions of the CH-FED resembled human fatty streaks with intracellular CE droplets. The lesions of the WHHL were morphologically similar to human advanced plaques, containing cholesterol monohydrate crystals as well as CE droplets. Diffuse intimal thickenings and massive lipid deposition developed in the ballooned iliacs of the CH-FED but not the WHHL, suggesting that factors in addition to hypercholesterolemia contribute to atherogenesis at the site of injury. The liver, spleen, and bone marrow were the organs most active in uptake of 3H-COE in the CH-FED, reflecting uptake by the β-VLDL receptor on macrophage-derived cells. In the WHHL, where lipoprotein uptake occurs only via low density lipoprotein-receptor independent mechanisms, the influx of radiolabel was greatest in the adrenal. The aortas of both CH-FED and WHHL were active in 3H-COE uptake. In autoradiographs (ARGs), the cells closest to the lumen at the time of injection were most active in plasma CE uptake. Mechanisms for the deposition of cells and lipid in the developing lesion were proposed based on the distribution of 3H-COE in ARGs. Both animals have hypercholesterolemia. However, the carriers of plasma CE, and time frame for progression of atherosclerosis are different, causing differences in the metabolism of plasma CE and the morphology and lipid content of atherosclerotic lesions.
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