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Plasma kinetics of free and esterified cholesterol in familial hypercholesterolemia: Effects of simvastatin

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Lipids

Abstract

The objective of this study was to evaluate the kinetics of both free and esterified forms of cholesterol contained in a emulsion that binds to LDL receptors (LDE) in subjects with heterozygous familial hypercholesterolemia (FH), and the same subjects under the effects of high-dose simvastatin treatment, as compared with a control normolipidemic group (NL). Twentyone FH patients (44.0±13.0 yr, 12 females, LDL cholesterol levels 6.93±1.60 mmol/L) and 22 normolipidemic patients (44.0±15.0, 10 females, LDL cholesterol levels 3.15±0.62 mmol/L) were injected intravenously with 14C-cholesteryl ester and 3H-cholesterol. FH patients were also evaluated after 2 mon of 40 or 80 mg/d simvastatin treatment, and plasma samples were collected over 24 h to determine the residence time (RT, in h) of both LDE labels, expressed as the median (25%; 75%). The RT of both 14C-cholesteryl ester and 3H-cholesterol were greater in FH than in NL [FH: 36.0 (20.5; 1191.0), NL: 17.0 (12.0–62.5), P=0.015; and FH: 52.0 (30.0; 1515.0); NL 20.5 (14.0–30.0) P<0.0001]. Treatment reduced LDL cholesterol by 36% (P<0.0001), RT of 14C-cholesteryl ester by 49% (P=0.0029 vs. baseline), and 3H-cholesterol RT by 44% (P=0.019 vs. baseline). After treatment, the RT values of 14C-cholesteryl ester in the FH group approached the NL values (P=0.58), but the RT of 3H-cholesterol was still greater than those for the NL group (P=0.01). The removal of LDE cholesteryl esters and free cholesterol was delayed in FH patients. Treatment with a high dose of simvastatin normalized the removal of cholesterol esters but not the removal of free cholesterol.

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Abbreviations

apo:

apolipoprotein

CAD:

coronary artery disease

FCR:

fractional catabolic rates

FH:

familial hypercholesterolemia

LDE:

cholesterol-rich emulsion

NL:

normolipidemic

PLTP:

phospholipid transfer proteins

RT:

residence time

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Authors and Affiliations

  1. Lipid Metabolism Laboratory and Lipid Clinic, The Heart Institute (InCor), University of São Paulo, Medical School Hospital (InCor-HCFMUSP), São Paulo, Brazil

    Raul D. Santos, Ana P. M. Chacra, Aleksandra Morikawa, Carmen C. Vinagre & Raul C. Maranhão

  2. Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil

    Raul C. Maranhão

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  1. Raul D. Santos
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  2. Ana P. M. Chacra
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  4. Carmen C. Vinagre
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Correspondence to Raul C. Maranhão.

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Santos, R.D., Chacra, A.P.M., Morikawa, A. et al. Plasma kinetics of free and esterified cholesterol in familial hypercholesterolemia: Effects of simvastatin. Lipids 40, 737–743 (2005). https://doi.org/10.1007/s11745-005-1437-6

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  • DOI: https://doi.org/10.1007/s11745-005-1437-6

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