Lecithin-cholesterol acyltransferase activity in normocholesterolaemic and hypercholesterolaemic roosters: modulation by lipid apheresis.

Lipid apheresis, a recently described procedure for the elimination of lipid but not apolipoproteins from plasma, was applied to normocholesterolaemic and hypercholesterolaemic roosters. Lipid apheresis resulted in an immediate reduction in plasma unesterified cholesterol concentration, which was sustained for 150 min. The reduction in unesterified cholesterol concentration was higher in the normocholesterolaemic animals than in the hypercholesterolaemic animals. Lipid apheresis induced changes in the ratio of plasma unesterified to total cholesterol in normocholesterolamic animals but not in hypercholesterolaemic animals. In hypercholesterolaemic animals, lecithin-cholesterol acyltransferase (LCAT) activity was not affected by lipid apheresis, whereas in normocholesterolaemic animals LCAT activity was acutely reduced for 150 min after lipid apheresis. Saturated LCAT kinetics occurred in the hypercholesterolaemic animals but not in the normocholesterolaemic animals. LCAT obeyed Michaelis-Menten kinetics. After lipid apheresis, there was a pool of unesterified cholesterol that was available as substrate for LCAT to a greater extent in hypercholesterolaemic animals than in normocholesterolaemic animals. These observations may have important implications for lipid apheresis as a treatment for atherosclerosis.

Lipid apheresis in an animal model causes in vivo changes in lipoprotein electrophoretic patterns.

Lipid apheresis, a new extracorporeal procedure based on plasma delipidation and showing promise as a possible treatment for atherosclerosis, was recently reported for the first time from this laboratory [Cham et al., J Clin Apheresis 10:61-69, 1995]. In the present study lipid apheresis was applied to hypercholesterolemic and normocholesterolemic roosters to examine its effect on plasma lipoprotein particles. This procedure resulted in conspicuous changes in electrophoretic patterns of plasma lipoproteins. The electrophoretic mobilities of all the lipoprotein fractions had changed considerably. Lipid stainable material was present in at least three bands in the alpha-globulin area. In particular, changes in the electrophoretic region of high-density lipoproteins were observed. Lipid apheresis markedly induced the anti-atherogenic pre- beta-high-density lipoproteins. The observed changes induced by lipid apheresis were more pronounced in the hyperlipidemic animals compared with the normocholesterolemic controls. A novel pre-alpha-lipoprotein band was observed soon after lipid apheresis. This lipoprotein band had a density larger than 1.21. At approximately 150 minutes after lipid apheresis, the electrophoretic pattern had almost returned to its original base pattern. Lipid apheresis results in plasma lipoprotein changes which may induce reverse cholesterol transport and shows promise as a possible treatment of atherosclerosis.

Lipid apheresis: an in vivo application of plasma delipidation with organic solvents resulting in acute transient reduction of circulating plasma lipids in animals.

Despite primary and secondary prevention of coronary disease with lowering plasma cholesterol by diet and drug therapy, coronary heart disease remains the major cause of death in Western countries. Low density lipoprotein apheresis had the potential to make a significant impact as it acutely leads to a marked reduction in plasma cholesterol. However, recent preliminary results suggest that low density lipoprotein apheresis may not be more effective in preventing progression of coronary disease than current drug therapy. We have devised a new technique, termed lipid apheresis, which removes cholesterol and triglycerides from plasma but retains the apolipoproteins. This procedure shows great promise in stimulating regression beyond current therapy. Lipid apheresis, a new extracorporeal procedure based on plasma delipidation with the organic solvent mixture butanol-diisopropyl ether, was applied to hypercholesterolemic and normocholesterolemic roosters. Approximately 25% of the calculated blood volume was removed from the animals. The plasma was separated from the blood cells. The plasma was delipidated for 20 min with the organic solvent mixture. The delipidated plasma containing all proteins, including the apolipoproteins and other ionic constituents, was remixed with the blood cells and infused back into the identical donor animals. Analyses of serial blood samples collected from lipid apheresed and sham treated animals up to 16 h after infusion revealed that lipid apheresis caused acute, marked reductions in plasma lipids. The pattern and extent of the plasma levels of cholesterol were different in the hypercholesterolemic animals when compared with normocholesterolemic animals, indicating that a readily extraplasma cholesterol pool in the hypercholesterolemic animals was rapidly mobilized into the plasma pool.(ABSTRACT TRUNCATED AT 250 WORDS)