title: Endothelial-derived lipoprotein lipase is bound to postprandial triglyceride-rich lipoproteins and mediates their hepatic clearance in vivo.
abstract: Lipoprotein lipase (LPL) is the key enzyme in the intravascular hydrolysis of triglyceride-rich lipoproteins (TRL). Furthermore, it has been shown that inactive LPL can mediate cellular binding and uptake of TRL in vitro. This study investigated whether LPL is bound to postprandial human TRL in vivo, and whether it plays a role in the hepatic clearance of these particles independent of its catalytic activity. LPL was found to bind to postprandial TRL in preheparin plasma of healthy young men. To study the effect of inactive LPL on particle uptake, TRL isolated from patients with inactive LPL (LPL or apoC-II mutations) were used before and after heparin administration. These model particles allow one to study the bridging effect of LPL independent of its enzymatic activity. Organ uptake studies with these particles in mice revealed that inactive LPL increases the hepatic clearance of TRL significantly while uptake into other organs remains largely unaffected. Further evidence that endothelial-derived LPL directs TRL to the liver in vivo was gained with transgenic mice that express inactive LPL exclusively in muscle, revealing greater hepatic uptake than in wild-type mice. In conclusion, these data demonstrate for the first time that LPL is a structural component of postprandial TRL which facilitates hepatic TRL clearance from the circulation independent of its catalytic function.
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. heeren@uke.uni-hamburg.de
authors.forename: Joerg
authors.initials: J
authors.lastname: Heeren
authors.forename: Andreas
authors.initials: A
authors.lastname: Niemeier
authors.forename: Martin
authors.initials: M
authors.lastname: Merkel
authors.forename: Ulrike
authors.initials: U
authors.lastname: Beisiegel
mesh_terms: D000328:Adult; D000818:Animals; D053304:Apolipoprotein C-II; D053318:Apolipoprotein E3; D001056:Apolipoproteins C / Q000097:blood / Q000172:deficiency / Q000235:genetics; D001057:Apolipoproteins E / Q000097:blood / Q000172:deficiency / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002417:Cattle; D002460:Cell Line; D002784:Cholesterol / Q000097:blood; D002914:Chylomicrons / Q000493:pharmacokinetics; D004730:Endothelium, Vascular / Q000201:enzymology*; D005838:Genotype; D006493:Heparin / Q000493:pharmacokinetics; D006801:Humans; D008071:Lipoprotein Lipase / Q000097:blood / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D009154:Mutation; D019518:Postprandial Period; D018110:Receptors, Lipoprotein / Q000378:metabolism; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D053304:Apolipoprotein C-II; D053318:Apolipoprotein E3; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D002914:Chylomicrons; D008074:Lipoproteins; D018110:Receptors, Lipoprotein; D014280:Triglycerides; D006493:Heparin; D002784:Cholesterol; D008071:Lipoprotein Lipase