Increased production of HDL ApoA-I in homozygous familial defective ApoB-100.
Familial defective apolipoprotein (apo) B-100 (FDB) is a frequent cause of hypercholesterolemia. Hypercholesterolemia in homozygous FDB is less severe than in homozygotes for familial hypercholesterolemia. Recently, we showed decreased low density lipoprotein (LDL) apoB-100 fractional catabolism and decreased production of LDL due to an enhanced removal of apoE-containing precursors in a patient with homozygous FDB. The effects of defective apoB-100 on high density lipoprotein (HDL) metabolism are unknown. We studied HDL apoA-I metabolism in this FDB patient and in 6 control subjects by using (2)H(3)-L-leucine as a tracer. ApoA-I levels were normal in all study subjects. However, the fractional catabolic rate and the production rate of apoA-I were increased, by 79% and 70%, respectively, in FDB; the fractional catabolic rate of apoA-I in FDB was 0.34 day(-1) compared with 0.19+/-0.03 day(-1) in normal controls. The production rate of apoA-I in FDB was 18.4 mg. kg(-1). d(-1) compared with 10.8+/-2.3 mg. kg(-1). d(-1) in controls. Thus, we have shown for the first time that defective apoB-100 may influence HDL kinetics. The increase in total HDL turnover might enhance reverse cholesterol transport and could contribute to the seemingly benign clinical course of FDB compared with that of familial hypercholesterolemia.
Schaefer
J R
JR
Department of Internal Medicine, Division of Cardiology, University of Marburg, Germany.
Winkler
K
K
Schweer
H
H
Hoffmann
M M
MM
Soufi
M
M
Scharnagl
H
H
Maisch
B
B
Wieland
H
H
Steinmetz
A
A
März
W
W
D000328:Adult; D016632:Apolipoprotein A-I / Q000096:biosynthesis* / Q000378:metabolism; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000235:genetics*; D001692:Biological Transport / Q000235:genetics; D005192:Family Health; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics* / Q000378:metabolism; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000096:biosynthesis* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000096:biosynthesis / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000096:biosynthesis / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014316:Tritium
D016632:Apolipoprotein A-I; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D014316:Tritium