Ratio Of Cholesteryl Ester Research Articles

Inter-relationship of lipids transferred by the lipid-transfer protein isolated from human lipoprotein-deficient plasma.

In a previous study we demonstrated that highly purified lipid-transfer protein facilitated the transfer of triglyceride, cholesteryl ester, and phosphatidylcholine between plasma lipoproteins. It remained unclear, however, whether these lipids were transferred by independent sites on the lipid-transfer protein. To address this point, we have studied the protein-mediated transfer of triglyceride, cholesteryl ester, and phosphatidylcholine as a function of the concentration and lipid composition of donor and acceptor lipoproteins. Lipoproteins labeled in vitro, reconstituted lipoproteins of defined lipid composition, and phosphatidylcholine liposomes with or without triglyceride and/or cholesteryl ester have been used to investigate the inter-relationships of lipids transferred by the lipid-transfer protein. In studies of initial (less than or equal to 10-13%) transfer, we found that, although absolute transfer rates were affected, the ratio of cholesteryl ester to triglyceride transferred was independent of donor and acceptor lipoprotein concentrations and acceptor lipoprotein lipid composition. With reconstituted lipoproteins as donor, we demonstrated that this ratio was linearly related to the ratio of cholesteryl ester to triglyceride in the donor particle; the sum of triglyceride and cholesteryl ester transferred remained constant and independent of the lipid composition of the donor. Experiments with intact lipoproteins labeled in vitro and with small unilamellar vesicles in the presence and absence of p-chloromercuriphenylsulfonate, confirmed the interdependence of triglyceride and cholesteryl ester transfer. In contrast, under all assay conditions, no correlation was found between the amount of phosphatidylcholine transferred and the transfer of triglyceride and/or cholesteryl ester. We conclude that triglyceride and cholesteryl ester compete for transfer and that the extent of transfer for each lipid is determined by its relative concentration in the donor particle, whereas phosphatidylcholine transfer is independent of triglyceride and cholesteryl ester transfer. The data also strongly support the conclusion that lipid transfer protein promotes both the exchange and net transfer of triglyceride and cholesteryl ester and that the net transfer process proceeds by a reciprocal exchange of triglyceride and cholesteryl ester without net transfer of core lipid between lipoproteins.

Cholesteryl ester and apolipoprotein E transfer between human high density lipoproteins and chylomicrons

The transfer of cholesteryl esters and apolipoprotein E has been studied between plasma HDL and chylomicrons isolated either from ascitic fluid or from the plasma of a patient with type V hyperlipoproteinemia. Whereas apolipoprotein E transfer was rapid and occurred at low temperature, cholesteryl ester transfer was suppressed at 4°C. Apolipoprotein E transfer did not depend upon the presence of cholesteryl ester transfer protein and was in fact inhibited by the partially purified preparation of this protein. Apolipoprotein E transfer was not increased by reduction with dithiothreitol. The transfer of cholesteryl esters increased sharply at a chylomicron to HDL ratio of cholesteryl ester above 1 10 , a value which may be of physiological significance at the peak of postprandial lipemia. At this ratio, the transfer of apolipoprotein E was minimal and increased only at ratios above 2 1 . From these results, it is concluded that there is no connection between apolipoprotein E and cholesteryl ester transfer from HDL to chylomicrons. It is, therefore, proposed that whereas chylomicron apolipoprotein E is acquired rapidly and mostly in the lymphatic system, the concentration of chylomicron cholesteryl esters increases significantly and independently in the circulation.

Heterogeneity of serum low density lipoproteins in normal human subjects.

Equilibrium density gradient ultracentrifugation of serum low density lipoprotein (LDL) from twelve healthy human subjects was used to separate six subfractions with mean density ranging from 1.0268 to 1.0597 g/ml. Mean corrected peak flotation rate (Sof) measured by analytic ultracentrifugation, and mean particle diameter determined by negative staining electron microscopy, both declined significantly with increasing density of the subfractions. Major differences in chemical composition of the subfractions were noted, including a significantly lower triglyceride content and higher ratio of cholesteryl ester to triglyceride in the middle fractions compared with those of highest and lowest density. Concentration of fraction 2 correlated positively with HDL (P less than 0.01) and negatively with VLDL (P less than 0.001); concentration of fraction 4 correlated negatively with HDL (P less than 0.05) and positively with VLDL (P less than 0.001) and IDL (P less than 0.01). LDL may thus include subspecies of differing structure and composition which might also have different metabolic and atherogenic roles.

Elevated cholesterol in tissues of chicken embryos with hereditary myotonic muscular dystrophy

The cholesterol content of muscle, liver, serum, and brain was examined both in embryos of chickens with hereditary muscular dystrophy and in normal control embryos between 9 and 16 days in ovo. The superficial pectoral muscles, which are severely affected by muscular dystrophy later in development, have a significantly higher cholesterol content than those of normal embryos at all ages examined. In contrast, the cholesterol content of thigh muscles that are not severely affected by the dystrophic process is no different from that of control embryos. The cholesterol contents of liver and serum from dystrophic embryos are also increased, but the cholesterol content of the brain is not. The increased cholesterol contents of liver and serum are due to proportionate increases of both free cholesterol and cholesteryl esters. In contrast, in superficial pectoral muscles the ratio of cholesteryl esters to free cholesterol is significantly increased. These data indicate that, in addition to the elevated cholesterol in the liver and serum of dystrophic embryos, the regulation of cholesteryl ester content in the dystrophic pectoral muscles is abnormal.