Human hepatic low-density lipoprotein receptors: associations of receptor activities in vitro with plasma lipid and apolipoprotein concentrations in vivo.
The relationships of plasma lipid and apolipoprotein (apo) concentrations to hepatic low-density lipoprotein (LDL) receptor activity were examined in 21 subjects (16 females, 5 males), who were undergoing laparotomy for non-neoplastic disease (cholecystectomy in 16). None had familial hypercholesterolemia, or renal, endocrine or hepatic disease. Ages were 37-77 years (mean, 58 years), plasma cholesterol concentrations 4.09-6.72 mmol/l (5.38) and plasma triacylglycerol concentrations 0.75-2.35 mmol/l (1.36). Receptor activity was quantified in vitro as the total saturable binding and EDTA-suppressible binding (representing apoB,E receptors) of 125I-labelled human LDL (15 micrograms protein/ml) by liver homogenate at 37 degrees C. There were no significant differences between men and women in 125I-labeled LDL binding. In the pooled data, EDTA-suppressible binding averaged 50 ng 125I-LDL protein/mg cell protein (S.D., 15). Total saturable binding averaged 2-fold greater (mean, 101 ng/mg; S.D., 32). Plasma cholesterol, LDL cholesterol and apoB concentrations were negative functions of both EDTA-suppressible binding and total saturable binding, but the correlations with EDTA-suppressible binding were stronger (cholesterol: r = -0.59, P less than 0.01; LDL cholesterol: r = -0.48, P less than 0.05; apoB: r = -0.61, P less than 0.01). Plasma triacylglycerol, high-density lipoprotein cholesterol and apoA-I concentrations were not related to either measure of receptor activity. These results provide evidence that the activity of apoB,E receptors in the liver is a major determinant of the plasma LDL concentration in middle-aged and elderly humans.
Nanjee
M N
MN
Department of Chemical Pathology and Metabolic Disorders, St. Thomas' Campus, United Medical School of Guy's Hospital, London U.K.
Miller
N E
NE
D000328:Adult; D000368:Aged; D000818:Animals; D016632:Apolipoprotein A-I; D001053:Apolipoproteins / Q000097:blood*; D001054:Apolipoproteins A / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D002417:Cattle; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004492:Edetic Acid / Q000494:pharmacology; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D008055:Lipids / Q000097:blood*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D051381:Rats; D011973:Receptors, LDL / Q000187:drug effects / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D001054:Apolipoproteins A; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007457:Iodine Radioisotopes; D008055:Lipids; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D014280:Triglycerides; D002784:Cholesterol; D004492:Edetic Acid