Density Lipoproteins In Rabbits Research Articles

Regulation of Plasma and Hepatic Lipids by Dietary Fatty Acids: Effects of Oleic, Elaidic and Palmitic Acids.

This study compares the effects of dietary oleic acid (OA), palmitic acid (PA), and trans fatty acids (TFA) on lipid metabolism in rabbits. Animals were fed semipurified diets in which a fifth of the fat intake (6% total energy) was either OA, PA, or TFA in the presence and absence of dietary cholesterol (0.2% w/w). After 10-12 weeks of feeding the cholesterol-free diets, there were no significant differences in plasma total cholesterol or triacylglycerol concentrations between groups. However, there was an increase in the cholesterol concentration of the lower density lipoproteins in rabbits fed the TFA diet compared with their OA- and PA-fed counterparts. The addition of dietary cholesterol had no effect on plasma lipids, however hepatic cholesterol concentrations were lower in animals fed the PA diet compared with those fed the OA diet (p<0.05), mainly due to a reduction in cholesteryl ester concentration (p<0.05). Despite these changes, hepatic low density lipoprotein (LDL)- receptor activity was not affected by diet. Palmitic and linoleic acids comprised similar proportions in the OA and TFA diets, however the proportion of hepatic phospholipid fatty acids as palmitic acid was lower (p<0.0001) while linoleic acid was higher (p<0.01) in animals fed TFA compared with those fed OA. These findings indicate that in rabbits fed dietary cholesterol (0.2%) TFA do not negatively impact on plasma lipids compared with either OA or PA. Also, increased esterification of TFA and linoleic acid to phospholipids at the expense of palmitic acid in animals fed TFA suggests that feeding TFA may result in cellular membranes with altered physical characteristics.

Enzymatic modification of plasma low density lipoproteins in rabbits: a potential treatment for hypercholesterolemia.

Phospholipase A2 (EC 3.1.1.4) hydrolyzes certain phospholipids of low density lipoprotein (LDL). Plasma clearance of phospholipase A2-modified human LDL is up to 17 times faster than that of native human LDL in hypercholesterolemic rabbits. Modification of blood lipoproteins of hypercholesterolemic rabbits was performed by using an extracorporeal circuit containing immobilized phospholipase A2. After 90-min treatments, nearly 30% decreases in plasma cholesterol concentrations were observed. Erythrocyte, leukocyte, and platelet counts showed no net change after treatment. This technique does not require any fluid replacement or sorbent regeneration and offers a potential approach for lowering serum cholesterol and LDL levels.

Extracorporeal Enzymatic Removal of Low Density Lipoproteins in Rabbits: Efficacy and Safety

An extracorporeal circuit incorporating a plasma separator reactor (PSR) was designed to modify low density lipoproteins (LDL). The PSR was tested in vivo with hypercholesterolemic New Zealand White rabbits. The bioreactor enzymatically converts LDL to a form that can be removed by the body at an enhanced rate. The physiological response of hypercholesterolemic New Zealand White rabbits to 90 minute extracorporeal treatments was monitored. The total plasma cholesterol concentration in the treated rabbits fell sharply (up to 40% decrease) during and following the treatment. Results of safety tests indicate no significant enzyme leaching from the device, no disruption or damage to erythrocytes, no increase in white blood cell count and no liver damage as indicated by five enzyme assays. All safety measurements suggest that the treatment is safe.

Effects of probucol on the in vivo plasma clearance of human low density lipoproteins in rabbits and on the expression of lipoprotein receptors in vitro

The purpose of this study was to investigate the effects of probucol on the plasma levels of low density lipoproteins in rabbits and whether the resulting decrease of low density lipoproteins was related to the effects of probucol on the expression of lipoprotein receptors. Probucol administration effectively lowered plasma cholesterol in normal rabbits. Both low density and high density lipoprotein cholesterol decreased, as well as apo B in the former fraction. Probucol had no effect on the fractional catabolic rate of low density lipoprotein while the flux of this lipoprotein decreased to about 50%. Moreover both the binding of lipoproteins to liver membranes and the in vitro uptake of low density lipoprotein by human skin fibroblasts were not affected by the drug. These findings are consistent with an effect of probucol on low density lipoprotein synthesis.

Receptor-independent catabolism of low density lipoprotein. Involvement of the reticuloendothelial system.

In this study we examine the effects of intravenous ethyl oleate emulsions on the metabolism of native and cyclohexanedione-modified human low density lipoprotein in rabbits. Treatment produced a highly significant fall in receptor-independent catabolism as measured by the fractional clearance rate of cyclohexanedione-modified low density lipoprotein. Receptor-dependent catabolism (the difference between the fractional clearance rates of native and cyclohexanedione-modified low density lipoprotein) was variably affected with some animals showing a decrease in receptor activity. These data suggest that the reticuloendothelial system makes a substantial contribution to receptor-independent low density lipoprotein catabolism in the rabbit.

Effects of cholestyramine on receptor-mediated plasma clearance and tissue uptake of human low density lipoproteins in the rabbit.

This study examines the effects of cholestyramine (2 g/day) on the plasma clearance and tissue uptake of human low density lipoprotein (LDL) in rabbits. 1,2-Cyclohexanedione modification of human LDL abolishes its recognition by high affinity cell membrane receptors in vitro and delays its plasma clearance in comparison to native LDL. Consequently, the difference between the fractional rates of catabolism of simultaneously injected native and cyclohexanedione-treated LDL is an index of in vivo receptor-mediated clearance of the lipoprotein. When human 125I-LDL and 131I-cyclohexanedione-treated LDL were injected into rabbits, 44% of the lipoprotein was cleared from the plasma by the receptor mechanism. Various tissues were removed from the animals at the end of the turnover study and their relative uptakes of 125I native and 131I-cyclohexanedione-treated LDL were measured. All exhibited receptor activity to some extent, incorporating more native than cyclohexanedione-modified LDL. The greatest receptor activity per g of tissue was found in lymph nodes, spleen, and liver and, in terms of whole organ uptake, the liver played a major role in LDL catabolism. Treatment of the rabbits with cholestyramine lowered the circulating LDL cholesterol level by promoting its clearance (120%, p < 0.001) via the receptor pathway. This was associated with a virtual doubling of receptor-mediated incorporation of the lipoprotein into the liver. These results suggest that the drain which cholestyramine induces in the hepatic cholesterol pool promotes LDL receptor activity in this organ and thereby lowers the level of circulating LDL.

Glycosaminoglycans inhibit the aortic uptake of very low density lipoproteins in rabbits

Summary The in vitro uptake of very low density lipoproteins obtained from cholesterol-fed rabbits (VLDL-HC) has been investigated in aortic tissue and in cultured smooth muscle cells, grown from thoracic aorta of normal rabbits. The incorporation of 125I-VLDL-HC into fragments of aortic tissue increased with the concentration of incubated lipoproteins, with incubation time, with the amount of incubated tissue, and appeared to be temperature-dependent. Heparin and a mixture of glycosaminoglycans extracted from pig duodenum inhibit the aortic uptake of lipoproteins and decrease both cell surface binding and internalization of VLDL-HC in cultured aortic smooth muscle cells. Cell monolayers increased their content in cholesterol esters when incubated in the presence of lipoprotein-carried cholesterol, and this accumulation was partially prevented by glycosaminoglycans. These results provide further evidence that the inhibition of lipoprotein uptake by arterial wall may contribute to the claimed antiarteriosclerotic properties of exogenously administered glycosaminoglycans.

PROCEEDINGS OF THE AUSTRALIAN SOCIETY FOR MEDICAL RESEARCH

PROCEEDINGS OF THE AUSTRALIAN SOCIETY FOR MEDICAL RESEARCH

Very low density lipoproteins in normal and cholesterol-fed rabbits: lipid and protein composition and metabolism: Part 1. Chemical composition of very low density lipoproteins in rabbits

The lipid and apoprotein composition of very low density lipoproteins (VLDL) ( d < 1.019 g/ml) from normal and hypercholesteremic (h.c.) rabbits are compared. Significant changes are observed in the apoproteins, as well as in the fatty acid composition of cholesterol esters, and in the relative distribution of phospholipids. Apoproteins show a marked increase of peptides with slow mobility (R2 and R3), corresponding to arginine-rich proteins, both in the rabbit and in some types of human hyperlipoproteinemias (hypothyroidism and Fredrickson Type III). VLDL were separated into the two fractions, VLDL-1 and VLDL-2. Peptides of slow mobility were shown to be present in a higher concentration in VLDL-1. Cholererol esters of h.c. VLDL have a very high content of oleic acid, the 18 : 1/18 : 2 ratio being about three times higher than in normal VLDL. Phospholipid distribution in h.c. VLDL is characterized by an increase of sphingomyelin and decrease of phosphatidylethanolamine. The PC/Sph ratio is about one fifth that of normal. These changes in VLDL lipids are very similar to those occurring in the lipid composition of the atherosclerotic plaques in mammals.

Very low density lipoproteins in normal and cholesterol-fed rabbits: lipid and protein composition and metabolism: Part 2. Metabolism of very low density lipoproteins in rabbits

The metabolic fate of very low density lipoproteins (VLDL) in normal and hypercholesteremic (h.c.) rabbits has been investigated. VLDL were labelled with 125I in the protein moieties and injected into normal and h.c. animals. The turnover of h.c. VLDL is markedly delayed as compared to that of normal VLDL, and conversion into lipoprotein classes of higher density is considerably decreased. This is observed when h.c. VLDL are injected either into h.c., or into normal rabbits. Arterial uptake of radioactivity is much higher with h.c. VLDL than with the normal lipoproteins, and it is highest when h.c. VLDL are injected into normal recipients. These data, together with those reported in the previous study, support the hypothesis that h.c. VLDL have an inherent atherogenicity. Injection of h.c. VLDL into normal animals also offers an experimental model for testing drugs or diets against atherosclerosis, using untreated animals.