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Effects of heparin on the uptake of lipoprotein lipase in rat liver.
Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Clinical Physiology.
Umeå University, Faculty of Medicine, Medical Biosciences, Physiological chemistry.
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2004 (English)In: BMC Physiology, ISSN 1472-6793, Vol. 4, no 1, 13- p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Lipoprotein lipase (LPL) is anchored at the vascular endothelium through interaction with heparan sulfate. It is not known how this enzyme is turned over but it has been suggested that it is slowly released into blood and then taken up and degraded in the liver. Heparin releases the enzyme into the circulating blood. Several lines of evidence indicate that this leads to accelerated flux of LPL to the liver and a temporary depletion of the enzyme in peripheral tissues. RESULTS: Rat livers were found to contain substantial amounts of LPL, most of which was catalytically inactive. After injection of heparin, LPL mass in liver increased for at least an hour. LPL activity also increased, but not in proportion to mass, indicating that the lipase soon lost its activity after being bound/taken up in the liver. To further study the uptake, bovine LPL was labeled with 125I and injected. Already two min after injection about 33 % of the injected lipase was in the liver where it initially located along sinusoids. With time the immunostaining shifted to the hepatocytes, became granular and then faded, indicating internalization and degradation. When heparin was injected before the lipase, the initial immunostaining along sinusoids was weaker, whereas staining over Kupffer cells was enhanced. When the lipase was converted to inactive before injection, the fraction taken up in the liver increased and the lipase located mainly to the Kupffer cells. CONCLUSIONS: This study shows that there are heparin-insensitive binding sites for LPL on both hepatocytes and Kupffer cells. The latter may be the same sites as those that mediate uptake of inactive LPL. The results support the hypothesis that turnover of endothelial LPL occurs in part by transport to and degradation in the liver, and that this transport is accelerated after injection of heparin.

Place, publisher, year, edition, pages
2004. Vol. 4, no 1, 13- p.
Keyword [en]
Animals, Cattle, Heparin/administration & dosage/*pharmacology, Injections, Lipoprotein Lipase/analysis/*metabolism/pharmacokinetics, Liver/*enzymology, Male, Protein Transport, Rats, Rats; Sprague-Dawley
URN: urn:nbn:se:umu:diva-15201DOI: 10.1186/1472-6793-4-13PubMedID: 15544705OAI: diva2:154873
Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2009-11-25Bibliographically approved
In thesis
1. Aspects on lipoprotein lipase and atherosclerosis
Open this publication in new window or tab >>Aspects on lipoprotein lipase and atherosclerosis
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Lipoprotein lipase (LPL) hydrolyses blood lipids at the vascular endothelium. This action makes fatty acids available for tissue metabolic requirements. LPL is anchored to the endothelium by electrostatic forces and may act as a bridge connecting lipoproteins to cell surfaces. Clusters of positively charged amino acid residues in LPL interact with anionic groups on oligosaccharides covering the cell surfaces. Heparin competes with cell surface oligosaccharides for binding to LPL. Interaction of LPL with soluble and cell surface- ound oligosaccharides influences the activity and catabolism of the enzyme. LPL has a dual role in the development of atherosclerosis. Hydrolysis of lipoproteins by LPL contributes to clearance of lipids from plasma, resulting in an anti-atherogenic lipid profile. On the other hand, trough its bridging function, LPL contributes to lipoprotein retention at the endothelium and in the connective tissue of the artery wall. Furthermore LPL may stimulate uptake of lipoproteins in cells, converting them to foam cells. In this way LPL is considered to be proatherogenic.

We have investigated the effects caused by a synthetic heparin analogue, RG-13577, developed for treatment of tumors by anti-angiogenesis theraphy (Paper I) and by heparin (Paper II) on the turnover and biological role of LPL. The variation of LPL activity in kidney among animal species was studied in Paper III. Localization of LPL in healthy and atherosclerotic human arteries in relation to two other heparin-binding proteins (extracellular superoxide dismutase and apolipoprotein B) was studied in Paper IV.

54 p.
National Category
urn:nbn:se:umu:diva-564 (URN)91-7305-8998 (ISBN)
Public defence
2005-09-07, sal E04, NUS, 09:00 (English)
Available from: 2005-08-18 Created: 2005-08-18 Last updated: 2009-10-13Bibliographically approved

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