Preferential clearance of apoB-48-containing lipoproteins after heparin-induced lipolysis is modulated by lipoprotein lipase activity.
The acute effects of intravenous heparin administration (50 U/kg body weight) on apolipoprotein (apo)B-48 and apoB-100-containing lipoproteins in relation to postheparin lipase activities were studied in ten healthy normolipidemic volunteers. Five subjects returned to receive sham injections with saline. Lipoproteins were separated from plasma by density gradient ultracentrifugation at baseline, 3, and 20 min postheparin. ApoB-48 and apoB-100 in d < 1.006 g/mL and 1.006 < d < 1.019 g/mL fractions were quantitatively measured after electrophoresis on 5% SDS polyacrylamide gels and Coomassie-blue staining. No significant changes were observed after saline injections. Heparin administration released lipoprotein lipase (LPL) and hepatic lipase (HL) activities after 20 min, and significantly reduced apoB-48 concentrations in d < 1.006 g/mL fractions only. ApoB-100 concentrations showed a trend to decrease in d < 1.006 g/mL fractions and to increase in 1.006 < d < 1.019 g/mL fractions. LPL activity was related to the percentual disappearance of apoB-48 (r = 0.81, P = 0.004) and apoB-100 (r = 0.91, P < 0.001) in d < 1.006 g/mL fractions. When little LPL was released (LPL activity < 120 mU/mL) by heparin, apoB-48 was preferentially eliminated over apoB-100. However, when abundant LPL was released (LPL activity > 140 mU/mL), comparable percentual reductions for apoB-48 and apoB-100 were seen. Pharmacokinetic analysis revealed first-order kinetics for the clearance of apoB-48 in d < 1.006 g/mL fractions, but zero-order kinetics for apoB-100 clearance. Under conditions of artificially enhanced lipolysis, the first catabolic step of apoB-48-containing lipoproteins and hepatic VLDL showed different pharmacokinetics. ApoB-48-containing lipoproteins were the preferred substrate for LPL, and only when abundant LPL was present, clearance of hepatic VLDL occurred.
van Beek
A P
AP
Department of Internal Medicine, University Hospital, Utrecht University, The Netherlands.
van Barlingen
H H
HH
de Ruijter-Heijstek
F C
FC
Jansen
H
H
Erkelens
D W
DW
Dallinga-Thie
G M
GM
de Bruin
T W
TW
D000293:Adolescent; D000328:Adult; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000097:blood*; D005215:Fasting; D005260:Female; D006207:Half-Life; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008049:Lipase / Q000097:blood; D008066:Lipolysis / Q000187:drug effects*; D008071:Lipoprotein Lipase / Q000097:blood*; D008074:Lipoproteins / Q000097:blood*; D008099:Liver / Q000201:enzymology; D008297:Male; D014280:Triglycerides / Q000097:blood
D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D008074:Lipoproteins; D014280:Triglycerides; D006493:Heparin; D008049:Lipase; D008071:Lipoprotein Lipase