The regulation of blood coagulation by high-density lipoprotein particles
type: CreativeWork
description: High-density lipoprotein (HDL) has anti-atherogenic properties and the plasma level of HDL cholesterol correlates inversely with the risk of coronary artery disease. The atheroprotective functions of HDL can be explained by its function in the reverse cholesterol transport. Blood coagulation is activated in response to tissue damage and involves a series of enzymatic protein complexes that assemble on the surface of anionic phospholipids, e.g. activated platelets. Lipoproteins contain a phospholipid surface, which may provide another phospholipid surface, other than platelets, that could stimulate the reactions of blood coagulation. Lipoproteins have been reported to have dual roles in the regulation of blood coagulation, therefore in this thesis the role of HDL in blood coagulation was investigated. HDL was studied in its ability to stimulate prothrombin activation. Anionic phospholipids lost their procoagulant function when incorporated into reconstituted HDL particles. The anionic phospholipids of these particles were unable to support binding to activated factor V (FVa). Serum was also shown to neutralize the procoagulant effect of anionic liposomes with transfer of phospholipids to both low-density lipoprotein (LDL) and HDL particles. The transfer of phospholipids was dependent on a catalytically active form of phospholipid transfer protein (PLTP). Total HDL, HDL3 and very high-density lipoprotein, all which contained endogenous PLTP, were all able to neutralize procoagulant liposomes. Addition of exogenous PLTP to either LDL or HDL2, which were both absent of endogenous PLTP, increased the neutralization of procoagulant liposomes. HDL has been reported to function as a cofactor to anticoagulant activated protein C (APC) in the degradation of FVa in the presence of protein S. HDL isolated by ultracentrifugation was found to stimulate the APC-mediated degradation of FVa. However, further purification of HDL by size-exclusion chromatography revealed that the stim…
abstract: High-density lipoprotein (HDL) has anti-atherogenic properties and the plasma level of HDL cholesterol correlates inversely with the risk of coronary artery disease. The atheroprotective functions of HDL can be explained by its function in the reverse cholesterol transport. Blood coagulation is activated in response to tissue damage and involves a series of enzymatic protein complexes that assemble on the surface of anionic phospholipids, e.g. activated platelets. Lipoproteins contain a phospholipid surface, which may provide another phospholipid surface, other than platelets, that could stimulate the reactions of blood coagulation. Lipoproteins have been reported to have dual roles in the regulation of blood coagulation, therefore in this thesis the role of HDL in blood coagulation was investigated. HDL was studied in its ability to stimulate prothrombin activation. Anionic phospholipids lost their procoagulant function when incorporated into reconstituted HDL particles. The anionic phospholipids of these particles were unable to support binding to activated factor V (FVa). Serum was also shown to neutralize the procoagulant effect of anionic liposomes with transfer of phospholipids to both low-density lipoprotein (LDL) and HDL particles. The transfer of phospholipids was dependent on a catalytically active form of phospholipid transfer protein (PLTP). Total HDL, HDL3 and very high-density lipoprotein, all which contained endogenous PLTP, were all able to neutralize procoagulant liposomes. Addition of exogenous PLTP to either LDL or HDL2, which were both absent of endogenous PLTP, increased the neutralization of procoagulant liposomes. HDL has been reported to function as a cofactor to anticoagulant activated protein C (APC) in the degradation of FVa in the presence of protein S. HDL isolated by ultracentrifugation was found to stimulate the APC-mediated degradation of FVa. However, further purification of HDL by size-exclusion chromatography revealed that the stim…
author: Oslakovic, Cecilia
language: eng
keywords: Medicinal Chemistry
date published: 2010
date modified: 2026-07-24T02:59:36Z
provider: University of Lund
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Department of Laboratory Medicine, Lund University