Plasma kinetics of free and esterified cholesterol in familial hypercholesterolemia: Effects of simvastatin |
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Authors: | Raul?D?Santos Ana?P?M?Chacra Aleksandra?Morikawa Carmen?C?Vinagre Email author" target="_blank">Raul?C?Maranh?oEmail author |
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Affiliation: | 1.Lipid Metabolism Laboratory and Lipid Clinic, The Heart Institute (InCor),University of S?o Paulo, Medical School Hospital (InCor-HCFMUSP),S?o Paulo,Brazil;2.Faculty of Pharmaceutical Sciences,University of S?o Paulo,S?o Paulo,Brazil |
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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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