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...

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Published in:Metabolism, clinical and experimental Vol. 50; no. 6; pp. 635 - 639
Main Authors: Fr[eacute]nais, R., Maugeais, C., Ouguerram, K., Za[iuml ]r, Y., Bard, J.M., Charbonnel, B., Magot, T., Krempf, M.
Format: Journal Article
Language:English
Published: New York, NY Elsevier Inc 01-06-2001
Elsevier
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Summary: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- 2H 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 [plusmn] 35 v 422 [plusmn] 27 mg/dL, P [lt ] .05, and 85 [plusmn] 19 v 327 [plusmn] 52 mg/dL, P [lt ] .05, respectively). Plasma triglyceride level was unaffected (162 [plusmn] 43 v 176 [plusmn] 35 mg/dL, not significant [NS]) and HDL composition remained stable (HDL-cholesterol 29 [plusmn] 6 v 37 [plusmn] 7 mg/dL, NS, and HDL-triglyceride 20 [plusmn] 6 v 19 [plusmn] 8 mg/dL, NS). Plasma apolipoprotein AI (apo AI) was also similar (122 [plusmn] 20 v 115 [plusmn] 18 mg/dL, NS). Mean HDL-apo AI fractional catabolic rate (FCR) was slightly higher (0.41 [plusmn] 0.07 v 0.36 [plusmn] 0.14 pool/d, NS), and absolute production rate (APR) was increased (22.1 [plusmn] 5.7 v 18.0 [plusmn] 5.7 mg/kg/d, P [lt ] .05) after LDL-apheresis. These human kinetic data suggest that LDL do not play a major role on HDL production in heterozygous FH patients.
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content type line 23
ISSN:0026-0495
1532-8600
DOI:10.1053/meta.2001.23285