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Title: Lipoproteins, blood coagulation and thrombosis
Author: Gray, E.
Awarding Body: CNAA
Current Institution: Open University
Date of Award: 1986
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The main aim of this study was to investigate the involvement of plasma lipoproteins in the blood coagulation system and the implications of this relationship in the pathogenesis of thrombosis. This study has shown that lipid peroxide-induced thrombin generation is caused by a two-fold mechanism: direct interaction of lipid peroxides with lipoprotein phospholipids and inhibition of anti-thrombin III via its heparin-binding site. Experiments using purified lipoproteins have shown that triglyceride-rich lipoproteins, i.e. chylomicra and very low density lipoproteins, are sources of procoagulant activity, whereas low density and high density lipoproteins have little effect. Further work with phospholipids extracted from chylomicra has demonstrated that lipid peroxides interact with the phospholipid component of the lipoprotein molecule and, possibly through an increase in overall negative charge, provide a suitable surface for the binding of clotting factors. Subcutaneous injection of potent lipase releasers, which are weak in vitro anticoagulants, reduce the ex vivo thrombin-generating activity of post-infusion plasma. This reduction in procoagulant activity is caused by the phospholipase action of the hepatic tri-glyceride lipase (HTGL) released. Human HTGL also enhances plasma anti-Xa activity, due to direct inhibition of Xa clotting activity, but the amidolytic activity of Xa is unaffected, thus implying that the serine site of Xa is not preferentially targeted. The phospholipid binding site of Xa appears to be involved, but this anti-Xa effect is not due to the phospholipase action of HTGL. The antithrombotic effects of heparin and heparin analogues may thus be partly due to the release of HTGL, which can reduce pro-coagulant activity via inhibition of lipid peroxide-induced thrombin generation and enhancement of plasma anti-Xa activity.
Supervisor: Not available Sponsor: National Institute for Biological Standards and Control
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Biochemistry Biochemistry Human physiology