Effect of low-density lipoproteins on apolipoprotein AI kinetics in heterozygous familial hypercholesterolemia.
In patients with heterozygous familial hypercholesterolemia (FH), both synthetic and clearance rates of high-density lipoproteins (HDL) are increased compared with control subjects. According to in vitro data on hepatocytes, the expanded pool size of low-density lipoproteins (LDL) in FH could partly explain the enhanced HDL production. Therefore, we have tested the hypothesis that a reduction of LDL pool size, achieved by LDL-apheresis, is associated with a downregulation of HDL synthesis. We studied the kinetics of HDL by infusing [5,5,5-(2)H(3)]-leucine in 7 heterozygous FH patients before and after 3 biweekly LDL-apheresis using dextran sulfate columns. Both plasma and LDL-cholesterol levels were decreased after LDL-apheresis (169 +/- 35 v 422 +/- 27 mg/dL, P <.05, and 85 +/- 19 v 327 +/- 52 mg/dL, P <.05, respectively). Plasma triglyceride level was unaffected (162 +/- 43 v 176 +/- 35 mg/dL, not significant [NS]) and HDL composition remained stable (HDL-cholesterol 29 +/- 6 v 37 +/- 7 mg/dL, NS, and HDL-triglyceride 20 +/- 6 v 19 +/- 8 mg/dL, NS). Plasma apolipoprotein AI (apo AI) was also similar (122 +/- 20 v 115 +/- 18 mg/dL, NS). Mean HDL-apo AI fractional catabolic rate (FCR) was slightly higher (0.41 +/- 0.07 v 0.36 +/- 0.14 pool/d, NS), and absolute production rate (APR) was increased (22.1 +/- 5.7 v 18.0 +/- 5.7 mg/kg/d, P <.05) after LDL-apheresis. These human kinetic data suggest that LDL do not play a major role on HDL production in heterozygous FH patients.
Frénais
R
R
Centre de Recherche en Nutrition Humaine, Groupe Métabolisme, Hôtel Dieu, Nantes, France.
Maugeais
C
C
Ouguerram
K
K
Zaïr
Y
Y
Bard
J M
JM
Charbonnel
B
B
Magot
T
T
Krempf
M
M
D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood / Q000378:metabolism*; D001781:Blood Component Removal; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000302:isolation & purification / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014316:Tritium
D016632:Apolipoprotein A-I; D008078:Cholesterol, LDL; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014316:Tritium; D002784:Cholesterol