Activity of low-density lipoprotein receptors as estimated from concentrations of apolipoprotein B and C-II in serum.
The correlation between low-density lipoprotein (LDL) receptor activity and concentrations of lipids and apolipoproteins in serum was examined in 12 subjects with heterozygous familial hypercholesterolemia (FH) and in four with non-FH type II hyperlipoproteinemia. Concentrations of high-density lipoprotein cholesterol and of apolipoproteins (apo) A-I, C-II, and C-III were significantly positively correlated with LDL receptor activity, whereas LDL receptor activity was significantly inversely correlated with LDL cholesterol and apo B concentrations, and with apo ratios B/A-I and B/A-II. Neither total serum cholesterol, triglyceride, phospholipid, apo A-I, nor apo E concentrations correlated significantly with LDL receptor activity. Multiple regression analysis, with LDL receptor activity as the dependent variable, revealed concentrations of apo B and apo C-II to be the principal determinant factors. To confirm this, we subsequently calculated the LDL receptor activities before and after administration of CS-514, an inhibitor of hydroxymethylglutaryl-CoA reductase (EC 1.1.1.88), which increases the hepatic LDL receptor activity and decreases the concentration of cholesterol in serum. This drug increased calculated LDL receptor activities significantly, with a significant decrease in serum cholesterol.
D053304:Apolipoprotein C-II; D001053:Apolipoproteins / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood*; D001056:Apolipoproteins C / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006938:Hyperlipoproteinemia Type II / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000494:pharmacology; D017035:Pravastatin; D011973:Receptors, LDL / Q000097:blood*
D053304:Apolipoprotein C-II; D001053:Apolipoproteins; D001055:Apolipoproteins B; D001056:Apolipoproteins C; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D009281:Naphthalenes; D011973:Receptors, LDL; D002784:Cholesterol; D017035:Pravastatin