In vivo metabolism of LDL subfractions in patients with heterozygous FH on statin therapy
| Autor: | H.C. Geiss, Carsten Otto, S. Bremer, P. H. R. Barrett, Klaus G. Parhofer |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Very low-density lipoprotein Apolipoprotein B low density lipoprotein metabolism Familial hypercholesterolemia QD415-436 Biochemistry chemistry.chemical_compound Endocrinology Internal medicine rebound kinetics medicine small dense low density lipoproteins density gradient ultracentrifugation biology familial hypercholesterolemia Chemistry Cholesterol low density lipoprotein subtypes Cell Biology Metabolism medicine.disease Apheresis LDL apheresis biology.protein Density gradient ultracentrifugation lipids (amino acids peptides and proteins) |
| Zdroj: | Journal of Lipid Research, Vol 45, Iss 8, Pp 1459-1467 (2004) |
| ISSN: | 0022-2275 |
| Popis: | LDL can be subfractionated into buoyant (1.020-1.029 g/ml(-1)), intermediate (1.030-1.040 g/ml(-1)), and dense (1.041-1.066 g/ml(-1)) LDLs. We studied the rebound of these LDL-subfractions after LDL apheresis in seven patients with heterozygous familial hypercholesterolemia (FH) regularly treated by apheresis (58 +/- 9 years, LDL-cholesterol = 342 +/- 87 mg/dl(-1), triglycerides = 109 +/- 39 mg/dl(-1)) and high-dose statins. Apolipoprotein B (apoB) concentrations were measured in LDL subfractions immediately after and on days 1, 2, 3, 5, and 7 after apheresis. Compartmental models were developed to test three hypotheses: 1) that dense LDLs are derived from the delipidation of buoyant and intermediate LDLs (model A); 2) that dense LDLs are generated directly from LDL-precursors (model B); or 3) that a model combining both pathways (model C) is necessary to describe the metabolism of dense LDLs. In all models, it was assumed that apoB production and fractional catabolic rate (FCR) did not change with apheresis. Apheresis decreased buoyant, intermediate, and dense LDL-apoB by 60 +/- 12%, 67 +/- 5%, and 69 +/- 11%, respectively. Models B and C, but not model A, described the rebound data. The model with the greatest biological plausibility (model C) was used to estimate metabolic parameters. FCR was 1.05 +/- 0.86 d(-1), 0.48 +/- 0.11 d(-1), and 0.69 +/- 0.24 d(-1) for buoyant, intermediate, and dense LDLs, respectively. Dense LDL production was 17.3 +/- 0.2 mg/kg(-1)/d(-1), 58% of which was derived directly from LDL precursors (VLDL, IDL, or direct secretion), while 42% was derived from buoyant and intermediate LDLs. Thus, our data indicate that in statin-treated patients with heterozygous FH dense LDLs originate from two sources. Whether this is also valid in other metabolic situations (with predominant small, dense LDLs) remains to be determined. |
| Databáze: | OpenAIRE |
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