Abstract
An elevated plasma cholesterol level is the primary riskfactor for coronary atherosclerosis (NCEP Report Summary 2001). In humans, most circulating cholesterol istransported in low-density lipoproteins (LDL). Between60% and 70% of circulating LDL is removed from thecirculation by LDL receptor (LDLR)-mediated endocytosis in the liver (Bilheimer et al. 1984; Goldstein et al.2001). Reductions in LDLR activity result in elevationsin plasma LDL-C and deposition of cholesterol in bodytissues (Goldstein et al. 2001). The critical importance ofthe LDLR pathway in preventing the accumulation ofLDL is illustrated by the very high plasma levels of LDLand severe, premature atherosclerosis that characterizesthe two autosomal dominant forms of Mendelian hypercholesterolemia: familial hypercholesterolemia (FH) andfamilial defective apolipoprotein B-100 (FDB)...
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