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Title: Studies on the effect of glycosaminoglycans on the release and activity of plasma triglyceride lipases
Author: Williams, Susan P.
Awarding Body: University of London
Current Institution: Royal Holloway, University of London
Date of Award: 1985
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The highly sulphated glycosaminoglycan (GAG) heparin is widely used clinically as an anticoagulant and antithranbotic. However, parenteral heparin, and also other anionic polysaccharides currently of interest as antithrombotics, release lipases from the capillary endothelium, resulting in clearing of circulating lipoproteins. These enzymes, lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) are released from the extra-hepatic and hepatic circulations respectively. A number of recognised lipase assay systems were compared and shown to vary considerably in their effectiveness and selectivity in measuring LPL and HTGL in post-heparin plasma (PHP). In an effort to determine what differences in polysaccharide structure influence lipase release, heparin and other GAGs and sulphated polysaccharides have been compared for their ability to release lipase after intravenous injection into rats. Molecular weight and charge density (degree of sulphation) were shown to be important, as well as some unknown factor associated with the heparin-heparan family of GAGs. Heparin was able to release approximately 50% more LPL than the other polysaccharides tested, but was only moderately more effective at releasing HTGL. No major differences could be found in the time courses of lipase release and clearance for the different polysaccharides. Purified LPL and HTGL were used to test the hypothesis that lipase release has a role in changing blood coagulability after injection of sulphated polysaccharides. HTGL was shown to have a significant effect on plasma anti-Xa clotting activities (by tests in vitro), to lengthen clotting times in the absence of heparin andto shorten them in its presence. The change induced by HTGL in the absence of heparin could be related positively to the lipoprotein content of the test plasmas, which is consistent with the proposed action of HTGL via lipoproteins. LPL had only a minimal effect, increasing clotting times slightly in both the presence and absence of heparin, and this may be due to the presence of contaminatory antithrombin III.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Biochemistry