Effects of atorvastatin on fasting plasma and marginated apolipoproteins B48 and B100 in large, triglyceride-rich lipoproteins in familial combined hyperlipidemia.
Large triglyceride (TG)-rich lipoproteins (TRLs) circulate in the blood, but they may also be present in a marginated pool, probably attached to the endothelium. It is unknown whether statins can influence this marginated pool in vivo in humans. Intravenous fat tests were performed in familial combined hyperlipidemia (FCHL) subjects before and after atorvastatin treatment and in controls to investigate whether acute increases in apoB in TRL fractions would occur, potentially reflecting the release of this TRL from a marginated pool. After a 12-h fast, a bolus injection of 10% Intralipid was given to 12 FCHL patients before and after 16-wk treatment with atorvastatin. Twelve carefully matched controls were included. For 60 min postinjection, apoB48, apoB100, and lipids were measured in TRLs. Fasting apoB100 in all TRL fractions were 2- to 3-fold higher in untreated FCHL compared with controls. ApoB48 concentrations in chylomicron fractions increased significantly within 10 min in FCHL before and after treatment, but not in controls. ApoB100 increased significantly in the chylomicron fractions in untreated FCHL and in controls, but not in FCHL after treatment. In very low density lipoprotein 1, apoB100 increased only in untreated FCHL. In very low density lipoprotein 2, apoB100 did not change in any group. These data show that increasing the number of circulating TRLs by chylomicron-like particles, results in increased plasma apoB-TRLs, probably by acute release from a marginated pool. This is a physiological process occurring in FCHL and in healthy normolipidemic subjects, but it is more pronounced in the former. Decreased marginated TRL particles in FCHL is a novel antiatherogenic property of atorvastatin.
Department of Internal Medicine, University Medical Center Utrecht, The Netherlands.
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Verseyden
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Meijssen
M Castro
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Cabezas
D000328:Adult; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000097:blood*; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D005215:Fasting; D005217:Fat Emulsions, Intravenous / Q000493:pharmacokinetics; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage*; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D006538:Heptanoic Acids; D011758:Pyrroles; D014280:Triglycerides; D002784:Cholesterol; D000069059:Atorvastatin