Low density lipoprotein metabolism in a family of familial hypercholesterolemic patients.
A low-density lipoprotein turnover study was performed on six heteroxygous familial hypercholesterolemic subjects and five control subjects. The diagnosis of the condition was clear-cut on biochemical, clinical, and genetic grounds. Kinetic analysis of the plasma decay curves gave the following mean values: (1) The plasma concentration of low density lipoprotein apoprotein (apoLDL) in the affected subjects was 247 mg/dl, a 2.5-fold increase over control values (98 mg/dl). (2) The calculated fractional catabolic rate of the intravascular apoLDL pool in the dyslipo-proteniemics was reduced with respect to control data (16.4%/day versus 31.2%/day), and the half-life of the apolipoprotein was correspondingly increased (6.07 days versus 3.63 days). (3) The absolute catabolic rate of the apoLDL was 15.6 mg/kg/day in contrast to the lower value of 11.6 mg/kg/day in the control group. (4) A strong negative correlation was observed between the plasma apoLDL concentration and the fractional catabolic rate (r = 0.96). We conclude from our data that increased apoLDL synthesis coupled with a defective or saturated catabolic mechanism is implicated in the pathogenesis of familial hypercholesterolemia.
D000328:Adult; D001059:Apoproteins / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D006579:Heterozygote; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged
D001059:Apoproteins; D008077:Lipoproteins, LDL; D002784:Cholesterol