Abstract
Epidemiologic and clinical data reveal the suprising fact that more than half of the people in industrialized societies have a level of circulating LDL that puts them at high risk for developing atherosclerosis. The more LDL in the blood, the more rapidly atherosclerosis develops (Goldstein and Brown 1982). However, we do not know yet the ideal level of cholesterol in the human blood. The plasma concentration levels of cholesterol now believed “normal” may well be too high in view of such a prevailing high risk of atherosclerotic lesions in industrialized societies. What determines the blood level of LDL? A specialized protein, called LDL receptor, plays an important role (Goldstein et al. 1983). The number of receptors on the surface of cells varies with the demand for cholesterol of the cells. When the need is low, the cells make fewer receptors and take up LDL at a reduced rate. This will protect cells against excess cholesterol, but at a high price: the reduction in the number of receptors decreases the rate at which LDL is removed from the circulation; the plasma level of LDL rises; and atherosclerosis is accelerated. The liver is a key organ in cholesterol and lipoprotein homeostasis, because of its large size and its high concentration of LDL receptors (Kita et al. 1982). It both synthesizes cholesterol (de novo synthesis) and acquires cholesterol from chylomicron remnants and other lipoproteins. Biliary excretion is the dominant pathway for net removal of cholesterol from the body. The bile acids are largely reabsorbed from the intestine, returned to the bloodstream, taken up by the liver and again secreted into the upper intestine.
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© 1987 Springer-Verlag Berlin Heidelberg
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Kita, T., Kume, N., Tsujita, Y., Ito, T., Watanabe, Y., Kawai, C. (1987). Induction of Hepatic Low-Density Lipoprotein Receptors in Heterozygous WHHL Rabbits Treated with CS-514 Alone or CS-514 in Combination with Cholestyramine. In: Paoletti, R., Kritchevsky, D., Holmes, W.L. (eds) Drugs Affecting Lipid Metabolism. Proceedings in Life Sciences. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-71702-4_47
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DOI: https://doi.org/10.1007/978-3-642-71702-4_47
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