Pathogenesis of Atherosclerosis
T. Kita
Dec 20, 1995
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Journal
Japanese Circulation Journal-english Edition
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Key Takeaway Key Takeaway: High levels of plasma cholesterol in humans increase the risk of atherosclerosis, and a new animal model, the WHHL-rabbit, has been developed to study the role of cholesterol metabolism in atherosclerosis development.
Abstract
Several epidemiologial studies reveal that more than half the people in industrialized societies have a high level of plasma cholesterol that puts them at high risk for developing atherosclerosis. The more cholesterol in the blood, the more rapidly atherosclerosis develops.’*2 However, we do not know yet the ideal level of cholesterol in human blood. The plasma levels of cholesterol now believed “normal” may well be too high in view of such a prevailing high risk of atherosclerotic lesions. What determines the blood level of cholesterol? The number of LDL receptors on the surface of cells varies with the demand for cholesterol of the c e k 3 Because of the size and the high concentration of LDL receptors, it is proved that liver is the key organ in cholesterol homeo~tasis.~ Especially in patients with familial hypercholesterolemia (FH), there are elevations of plasma cholesterol level and premature coronary atherosclerosis because of decreased activity or deficiency of the LDL re~eptor .”~ In autopsy specimens of FH patients, the characteristic feature of the early stage of atherosclerosis is the migration and accumulation of macrophages in the subendothelial spaces and the conversion of macrophages into foam cells. Studies of lipoprotein metabolism in macrophages were initiated to explain the paradoxical finding that even FH patients who have no LDL receptor can accumulate lipoprotein-bound cholesteryl esters in macrophages. A new animal model of human FH, known as the Watanabe heritable hyperlipidemic (WHHL) rabbit, has recently become a~ai lab le .~ .~-* Homozygous WHHL-rabbits resemble their human counterparts in having an accumulation of very low density lipoprotein (VLDL) and LDL on a low-fat diet, severe fulminant atherosclerosis, and a genetic defect