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Increased clearance of low density lipoprotein precursors in patients with heterozygous familial defective apolipoprotein B-100: a stable isotope approach.
J Lipid Res. 1996 Oct; 37(10):2074-87.JL

Abstract

In familial defective apolipoprotein B-100 (FDB) the presence of a mutant apolipoprotein (apo) B-100 (FDB3500Q/W) in LDL markedly reduces their affinity for the LDL receptor, leading to elevated LDL cholesterol levels. However, the hypercholesterolemia in most FDB patients is relatively mild when compared with, e.g., familial hypercholesterolemia (FH). In order to study mechanisms that may partly alleviate the clinical consequences of FDB, we investigated the in vivo kinetics of apoB-100-containing lipoproteins in five FDB heterozygotes (total cholesterol: 7.84 +/- 1.37 mmol/I; total apoB: 1.68 +/- 0.37 g/l; mean +/- SD) and six normolipidemic controls (4.61 +/- 0.62 mmol/l; 0.98 +/- 0.12 g/l) using a stable isotope approach. During and after a 10-12 h primed, constant infusion of either [13C6]phenylalanine or [2H3]leucine, tracer enrichment was determined in apoB-100 from ultracentrifugally isolated VLDL1 (Sf 60-400), VLDL2 (Sf 20-60), IDL (Sf 12-20), LDL1 (Sf 7-12), and LDL2 (Sf 0-7). The rates of apoB-100 production, catabolism, and transfer were estimated by model-based compartmental analysis. The overall fractional catabolic rate (FCR) of IDL apoB-100 in FDB was substantially increased (2.99 +/- 0.68 pools/day vs. 1.70 +/- 0.23 pools/day in controls, P < 0.01). The fractional rate of apoB-100 transfer from IDL to LDL in FDB was decreased (0.97 +/- 0.13 pools/day vs. 1.24 +/- 0.10 pools/day, P < 0.05). The FCR of LDL apoB-100 in FDB was decreased (0.18 +/- 0.07 pools/day vs. 0.56 +/- 0.05 pools/, P < 0.01). Finally, the input rate of LDL apoB-100 in FDB was markedly decreased (9.45 +/- 2.96 mg/kg day1 vs. 15.54 +/- 1.70 mg/kg day1, P < 0.05). Our data suggest that the relatively small increase of LDL concentrations in FDB is due to an increased clearance of LDL precursor particles via the LDL-receptor and apoE-receptors as well as a decreased conversion of IDL to LDL - two mechanisms that distinguish FDB from FH.

Authors+Show Affiliations

Institute and Policlinic of Clinical Metabolic Research, Medical Faculty "C.G. Carus', Technical University, Dresden, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8906585

Citation

Pietzsch, J, et al. "Increased Clearance of Low Density Lipoprotein Precursors in Patients With Heterozygous Familial Defective Apolipoprotein B-100: a Stable Isotope Approach." Journal of Lipid Research, vol. 37, no. 10, 1996, pp. 2074-87.
Pietzsch J, Wiedemann B, Julius U, et al. Increased clearance of low density lipoprotein precursors in patients with heterozygous familial defective apolipoprotein B-100: a stable isotope approach. J Lipid Res. 1996;37(10):2074-87.
Pietzsch, J., Wiedemann, B., Julius, U., Nitzsche, S., Gehrisch, S., Bergmann, S., Leonhardt, W., Jaross, W., & Hanefeld, M. (1996). Increased clearance of low density lipoprotein precursors in patients with heterozygous familial defective apolipoprotein B-100: a stable isotope approach. Journal of Lipid Research, 37(10), 2074-87.
Pietzsch J, et al. Increased Clearance of Low Density Lipoprotein Precursors in Patients With Heterozygous Familial Defective Apolipoprotein B-100: a Stable Isotope Approach. J Lipid Res. 1996;37(10):2074-87. PubMed PMID: 8906585.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased clearance of low density lipoprotein precursors in patients with heterozygous familial defective apolipoprotein B-100: a stable isotope approach. AU - Pietzsch,J, AU - Wiedemann,B, AU - Julius,U, AU - Nitzsche,S, AU - Gehrisch,S, AU - Bergmann,S, AU - Leonhardt,W, AU - Jaross,W, AU - Hanefeld,M, PY - 1996/10/1/pubmed PY - 1996/10/1/medline PY - 1996/10/1/entrez SP - 2074 EP - 87 JF - Journal of lipid research JO - J. Lipid Res. VL - 37 IS - 10 N2 - In familial defective apolipoprotein B-100 (FDB) the presence of a mutant apolipoprotein (apo) B-100 (FDB3500Q/W) in LDL markedly reduces their affinity for the LDL receptor, leading to elevated LDL cholesterol levels. However, the hypercholesterolemia in most FDB patients is relatively mild when compared with, e.g., familial hypercholesterolemia (FH). In order to study mechanisms that may partly alleviate the clinical consequences of FDB, we investigated the in vivo kinetics of apoB-100-containing lipoproteins in five FDB heterozygotes (total cholesterol: 7.84 +/- 1.37 mmol/I; total apoB: 1.68 +/- 0.37 g/l; mean +/- SD) and six normolipidemic controls (4.61 +/- 0.62 mmol/l; 0.98 +/- 0.12 g/l) using a stable isotope approach. During and after a 10-12 h primed, constant infusion of either [13C6]phenylalanine or [2H3]leucine, tracer enrichment was determined in apoB-100 from ultracentrifugally isolated VLDL1 (Sf 60-400), VLDL2 (Sf 20-60), IDL (Sf 12-20), LDL1 (Sf 7-12), and LDL2 (Sf 0-7). The rates of apoB-100 production, catabolism, and transfer were estimated by model-based compartmental analysis. The overall fractional catabolic rate (FCR) of IDL apoB-100 in FDB was substantially increased (2.99 +/- 0.68 pools/day vs. 1.70 +/- 0.23 pools/day in controls, P < 0.01). The fractional rate of apoB-100 transfer from IDL to LDL in FDB was decreased (0.97 +/- 0.13 pools/day vs. 1.24 +/- 0.10 pools/day, P < 0.05). The FCR of LDL apoB-100 in FDB was decreased (0.18 +/- 0.07 pools/day vs. 0.56 +/- 0.05 pools/, P < 0.01). Finally, the input rate of LDL apoB-100 in FDB was markedly decreased (9.45 +/- 2.96 mg/kg day1 vs. 15.54 +/- 1.70 mg/kg day1, P < 0.05). Our data suggest that the relatively small increase of LDL concentrations in FDB is due to an increased clearance of LDL precursor particles via the LDL-receptor and apoE-receptors as well as a decreased conversion of IDL to LDL - two mechanisms that distinguish FDB from FH. SN - 0022-2275 UR - https://www.unboundmedicine.com/medline/citation/8906585/Increased_clearance_of_low_density_lipoprotein_precursors_in_patients_with_heterozygous_familial_defective_apolipoprotein_B_100:_a_stable_isotope_approach_ L2 - http://www.jlr.org/cgi/pmidlookup?view=long&amp;pmid=8906585 DB - PRIME DP - Unbound Medicine ER -