The effect of lipid peroxidation and lipolysis on the ability of lipoproteins to influence thromboplastin activity.
High, low and very low density lipoproteins and lipoprotein (a) were prepared from porcine serum. The apolipoprotein components of the lipoproteins were then isolated and resuspended in soybean lecithin. Apolipoprotein B was also resuspended in lipids more representative of those found in LDL and VLDL. Lipid peroxidation was induced in samples of all the lipoproteins and reconstituted apolipoproteins by incubation with either Cu2+ ions or hedgehog 15-lipoxygenase. Furthermore, aliquots of the samples were incubated with a mixture of lipases. The effect of native preparations and the treated samples on the procoagulant activity of thromboplastin was examined. Native HDL, apo A-II, native LDL, reconstituted LDL and apo B inhibited thromboplastin activity, whereas native VLDL and reconstituted VLDL enhanced this activity. While the ability of HDL and apolipoprotein A-II to inhibit thromboplastin was unaltered by either Cu2+ oxidation, lipoxygenase oxidation or lipolysis, VLDL and particles resembling VLDL, which acted cooperatively with thromboplastin lost their activating potential. On the other hand, LDL and particles resembling LDL changed from being inhibitory to enhancing the thromboplastin activity following oxidation, but not after lipolysis. Apolipoprotein B fragments obtained by mild digestion of this protein, expressed an inhibitory effect towards thromboplastin, while extensive degradation of the protein reduced its inhibitory potential. It is suggested that modifications of lipoproteins in vivo can lead to a hypercoagulable state by modulation of the cofactor activity of thromboplastin to factor VII.
Ettelaie
C
C
Department of Biochemistry and Molecular Biology, Royal Free Hospital School of Medicine, London, UK.
Howell
R M
RM
Bruckdorfer
K R
KR
D000818:Animals; D006364:Hedgehogs; D015227:Lipid Peroxidation; D008066:Lipolysis; D008074:Lipoproteins / Q000378:metabolism / Q000502:physiology*; D013552:Swine; D013925:Thromboplastin / Q000037:antagonists & inhibitors / Q000502:physiology*
D008074:Lipoproteins; D013925:Thromboplastin