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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the metabolism of different classes of lipoprotein in squirrel monkeys and rabbits. Lipoproteins were labeled in vivo in donor animals with (3H)leucine and (3H)cholesterol. The rate of disappearance from plasma of recipient squirrel monkeys of the protein moiety of the very low density lipoproteins was rapid, that of high density lipoproteins slow, and the rate for low density lipoproteins was intermediate. The fractional turnover of the apoprotein of low density lipoproteins was slightly reduced in hyperlipidemic monkeys, but the absolute rates of synthesis and catabolism were increased. Hyperdipidemia in rabbits resulted in a dramatic reduction in the fractional catabolic rate of low density lipoprotein apoprotein. Hyperlipidemia in the donors of biosynthetic low density lipoproteins also influenced the rates of catabolism in rabbits. We showed the cycloheximide that although there was recycling of (3H)leucine into other proteins, the reutilization of leucine from low density lipoproteins for nascent low density lipoproteins was not significant. In most tissues the ratio of cholesterol:protein radioactivity was much greater than that for plasma 24 h after administration of labeled low density lipoproteins, but the ratios for aortic intima plus inner media and for plasma low density lipoproteins were similar. The presence of atherosclerosis resulted in a large increase in the apparent uptake of low density lipoproteins by the aortas of rabbits and monkeys.
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PMID:The effects of hyperlipidemia on lipoprotein metabolism in squirrel monkeys and rabbits. 16 56

Methods for quantitation of the major apoproteins of human serum very low density lipoprotein have been developed employing tetramethylurea, which delipidates the lipoprotein and selectively precipitates apolipoprotein B. Six soluble apoproteins are separated by electrophoresis in polyacrylamide gel. One of these is a previously unrecognized species of R-alanine (R4-alanine), more anionic than the R3-alanine polypeptide. Conditions of staining have been found which yield reproducibly linear chromogenic response with native lipoprotein and with each purified apoprotein. Recovery of protein in the seven species measured accounts for over 97% of the total in the very low density lipoprotein of normolipidemic individuals and in most samples from individuals with endogenous hyperlipemia. The mean content of apolipoprotein B in 43 samples from normolipidemic subjects was 36.9(+/-1.2 SEM)% of total protein, The distribution of the major soluble apoproteins as mean (+/-SEM) percentage of the soluble fraction was : R-serine, 5.3+/-o.5; arginine-rich, 20.6+/-1.0; R-glutamic, 10.6+/-0.4; R2-alanine, 28.3+/-0.7; R3-alanine, 26.9+/-0.5; and R4-alanine, 8.0+/-0.5. Distribution of the apoproteins was a function of particle diameter of very low density lipoprotein in fractions separated by gel permeation chromatography and by density gradient ultracentrifugation. In fractions below 700-800 A, apolipoprotein B comprised an increasing percentage of the total protein with decreasing particle diameter. Among the soluble proteins the percentage of the arginine-rich and R-serine polypeptides increased and that of the R-glutamic polypeptide declined progressively with decreasing particle size. Apoprotein distribution was similar in fractions of similar particle size from normolipidemic and hyperlipemic subjects with the exception that all fractions from the hyperlipemic subjects contained more R-serine and some, more arginine rich polypeptide. Even in the absence of chylomicrons, the distribution of soluble apoproteins in particles of diameters greater than 700-800 A was usually similar to that of the smallest particles. This suggests that the largest particles may include products of the partial catabolism of chylomicrons.
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PMID:Apoprotein composition of very low density lipoproteins of human serum. 17 34

The metabolism of lipoprotein-apoprotein was examined in four subjects with normal lipid metabolism and in one subject with type II hyperlipemia by means of isotopic tracer methodology. Studies were performed after intravenous injection of a radioactive amino acid precursor for apoprotein synthesis (75Se-selenomethionine), in both the basal state and following the acute injection of intravenous heparin. Computer technics were used to evaluate a series of multicompartmental models, and a general model is proposed that yields optimum fitting of experimental data for serum free amino acid precursor, very-low-density lipoprotein-apoprotein (VLD-apoprotein), and low-density lipoprotein-apoprotein (LDL-apoprotein) in man. The analysis demonstrates that approximately half of the transport of 75Se-apoVLDL from the plasma VLDL pool is converted to 75Se-apoLDL. The acute injection of heparin in two normal subjects results in a two-and-a-half-fold increase in this rate of conversion of 75Se-apoVLDL to 75Se-apoLDL. 75Se-apoLDL is metabolized by rapid transport into a recycling extravascular pool and by irreversible catabolism. The fractional rate of recycling is large relative to the fractional rate of catabolism of apoLDL (3.7:1.0), suggesting extravascular recycling as a potential site of regulation of the plasma concentration of apoLDL. In a patient with type II hyperlipemia, the extravascular recycling pathway is reduced and is not corrected with D-thyroxine therapy. However, this therapy did reduce conversion of apoVLDL to apoLDL in this type II patient. The kinetic data support the validity of the compartmental model in simulating both normal and pathologic apoprotein metabolism and that perturbation of physiology seen with heparin injection and D-thyroxine therapy. These data support a quantitative role of apoVLDL as a precursor of apoLDL and identify an important recycling pathway of apoLDL metabolism in addition to that of catabolism.
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PMID:Incorporation of 75Se-selenomethionine into human apoproteins. III. Kinetic behavior of isotopically labeled plasma apoprotein in man. 18 7

Because the cholesterol-rich very low density (VLD) lipoproteins of subjects with type III hyperlipoproteinemia are distinctively enriched in apolipoprotein E, a radial immunodiffusion assay for apolipoprotein E in whole plasma was developed. Its diagnostic usefulness was tested in randomly selected (n = 174) and hyperlipidemic (n = 61) subsets of an adult employee population and a hyperlipidemia clinic referral group (n = 63), which included 18 patients with well-documented type III hyperlipoproteinemia. Apolipoprotein-E levels were normally distributed among the random population subset, were equal between the two sexes, and increased little with age. The mean and 99th percentile values were 24.6 and 40.1 mg/dl, respectively. All subjects with type III patterns as assigned by standard criteria from both population (n = 4) and referral sources exceeded this 99th percentile (chi +/- SD = 54.7 +/- 9.7 mg/dl). Hence a plasma apolipoprotein-E concentration exceeding 40 mg/dl appears diagnostic of type III hyperlipoproteinemia, representing the first application of an apolipoprotein immunoassay to improved diagnosis of the hyperlipoproteinemias.
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PMID:Type III hyperlipoproteinemia: diagnosis in whole plasma by apolipoprotein-E immunoassay. 20 Jan 60

To determine whether human small intestine synthesizes apoA-I, the major apoprotein of plasma high-density lipoproteins, we used immunofluorescence technics and monospecific antiserums to visualize apoA-I within intestinal epithelial cells from four normal subjects and one patient with Tangier disease. Biopsies from all subjects during fasting showed limited fluorescence. After lipid feeding intracellular apoA-I markedly increased in both normal subjects and the patient. During alimentary lipemia, mean plasma apoA-I levels (milligrams per deciliter) increased in four normal subjects from 161 +/- 12 (+/- S.E.M.) to 180 +/- 15 (P less than 0.05) and in the patient from 1.9 to 6.8. Normal plasma chylomicrons contained apoB, apoE and the C peptides but not apoA-I. The patient's chylomicrons contained ap0A-I. Normal and Tangier-disease intestinal-mucosa cells increase their content of apoA-I during chylomicron formation and subsequently contribute to plasma apoA-I levels. The low levels of apoA-I in Tangier disease are not due to a failure of intestinal synthesis but might be due to abnormal metabolism of chylomicron apoproteins.
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PMID:Apoprotein A-I synthesis in normal intestinal mucosa and in Tangier disease. 21 20

The influence of cortisol (5 mg/kg body wt administered daily for 5 and 10 days) on biosynthesis of apoproteins of lipoproteins of very low density in the liver and on the synthesis of apolipoproteins of very low, low, and high density (VLDL, LDL, and HDL apoproteins, respectively) in the blood serum of adrenalectomized animals, and after replacement cortisol therapy was studied. Cortisol treatment during these periods resulted in the VLDL apoproteins biosynthesis inhibition in the rat liver. The synthesis of apolipoproteins was increased by adrenalectomy; this effect was eliminated after replacement cortisol treatment. The apoprotein synthesis was stimulated within 5 hours by single injection of cortisol or ACTH. Study of the blood serum apolipoproteins specific radioactivity indicated metabolic change of lipoproteins, such as disturbed conversion from VLDL to LDL. Single and prolonged cortisol administration led to the opposite results. The authors believe that the metabolic disturbances of lipoproteins in the blood play a more important role in the pathogenesis of cortisol-induced hyperlipidemia than lipoprotein syntesis stimulation in the liver.
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PMID:[Cortisol, adrenocorticotropic hormone and apolipoprotein synthesis in rat hepatocytes]. 21 82

Under in vivo conditions cortisol induces moderate hyperlipidemia followed by an increase in the phospholipid and triglyceride concentrations in the blood and a decrease of cholesterol; similar changes were observed in the liver. At all time intervals studied cortisol inhibits the phospholipid and cholesterol syntheses and decreases the specific radioactivities of the lipids in the mitochondrial fraction. The hormone has an inhibiting effect on the fatty acid synthesis at early postinjection stages. The phospholipid synthesis is increased after adrenalectomy and is then inhibited after injection of the hormone. A single injection of ACTH or cortisol causes suppression of phospholipid and cholesterol syntheses and a decrease in their specific radioactivities in the mitochondria. A similar effect is observed under stress conditions. In addition, the hormone inhibits the synthesis of lipoprotein apoproteins of very low and high densities. After 5 hours following the hormone injection the lipoprotein apoprotein synthesis in the liver is activated; the activation of apoprotein synthesis is also observed after adrenalectomy. However, the injection of the hormone to adrenalectomized rats decreases the apoprotein synthesis. It was shown that in blood serum cortisol affects the conversions of very low density lipoproteins into low density lipoproteins, thus providing for hyperlipidemia.
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PMID:[Effects of cortisol on lipid and lipoprotein synthesis in rat hepatocytes]. 21 25

The plasma lipoproteins of estrogen-treated and untreated sexually immature hens have been compared with respect to their concentration in plasma, protein and lipid composition, particle size, and and apoprotein composition. Administration of diethylstilbestrol resulted in a 400-fold rise in the concentration of very low density lipoprotein (VLDL), a 70-fold rise in low density lipoprotein (LDL), and a marked reduction in high density lipoprotein (HDL) protein. It also resulted in the production of LDL and HDL which were enriched in triacylglycerol, while the proportion of cholesterol in all three lipoprotein fractions decreased. In contrast to the lipoproteins from untreated birds, lipoproteins of density less than 1.06 g/ml from estrogen-treated birds were not clearly separable into discrete VLDL and LDL fractions, but appeared to be a single ultracentrifugal class. The apoprotein composition of VLDL and LDL from untreated birds differed from each other; however, the apoprotein patterns of VLDL and LDL from estrogen-treated birds were indistinguishable: both contained a large amount of low molecular weight protein in addition to the high molecular weight component that predominates in the untreated state. The apoprotein composition of HDL was also markedly altered by estrogen administration: the 28,000 mol. wt. protein (apo A-I) decreased in amount from 65% to less than 5% of the total, while a low molecular weight (Mr = 14,000) protein and as yet poorly defined high molecular weight components became predominant. These observations indicate that the hyperlipidemia induced by estrogen administration is accompanied by marked alterations, both qualitative and quantitative, in the plasma lipoproteins.
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PMID:Effects of estrogen administration on the lipoproteins and apoproteins of the chicken. 21 32

Four subfractions of plasma VLDL characterized by decreasing Sf value and LDL were isolated by density gradient preparative ultracentrifugation from normotriglyceridemic (NTG) and hypertriglyceridemic (HTG) (type IV) subjects in the fasting state and after a fatty meal. Chemical analysis and computation of numbers of particles in each fraction showed that the hyperlipidemia of type IV subjects was accounted for by an increase in total numbers of VLDL and a shift in the distribution of VLDL towards particles of larger diameter. Postprandial hyperlipidemia was due to the presence of chylomicron remnants rather than intact chylomicrons, and was accounted for by an increase in particle diameter of the largest VLDL subfraction rather than by an increase in particle numbers. Postprandial hyperlipedemia was accompanied by a shift in the distribution of VLDL towards particles of larger diameter in both NTG and HTG subjects, probably because of competition for the triglyceride-depletion process between chylomicrons and hepatic VLDL. Most chylomicron remnants were removed from the circulation without degradation to smaller VLDL or to LDL, but some remnants were sufficienty small to contribute to smaller VLDL subfractions. The LDL of type IV subjects contained more apoprotein B than those from NTG subjects, and this difference was associated with increases in diameter, molecular weight, density, and the ratio of protein: phospholipid in LDL from type IV subjects. Defective degradation of large VLDL to small VLDL, and of VLDL to LDL may be related to this alteration in apoprotein B content of the lipoproteins in type IV subjects.
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PMID:Changes in plasma very low density and low density lipoprotein content, composition, and size after a fatty meal in normo- and hypertriglyceridemic man. 22 Mar 59

Some of the component moieties of high density lipoproteins (HDL) were analyzed in normal subjects and in patients with hyperlipidemia. Apoproteins A-I and A-II were quantified by radioimmunoassay, HDL cholesterol and triglycerides were assessed on heparin-MnCl2 supernates of fasting plasmas. We found that HDL is enriched in triglycerides in all forms of hyperlipidemia, while the proportion of ApoA-II is unaltered and the proportion of ApoA-I is decreased. Thus, the composition of HDL is altered in hupertirglyceridemia. The molecular associations of ApoA-I and ApoA-II in plasma were also examined by assaying the apoprotein contents of plasma fractions prepared by ultracentrifugation and by gel filtration column chromatograpy. The ApoA-I contents of d smaller than 1.063 fraction increased in hyperlipidemia from smaller than 0.5% to approximately 2%, but the ApoA-I contents of the d greater than 1.21 fraction remained at less than 12% of total plasmas with triglyceride levels smaller than 1500 mg/dl. d greater than 1.21 ApoA-I rose to 23% in one plasma with a triglyceride level of greater than 1700 mg/dl. On column chromatography, ApoA-I eluted with the lipoproteins and also in a fraction whose molecular weight (MW) appeared to be approximately 50,000 daltons. The proportion of plasma ApoA-I which eluted in the 50,000 MW peak was positively correlated with plasma triglyceride levels, but at triglyceride levels of less than 1500 mg/dl, less than 20% of ApoA-I was in the 50,000 MW peak. Between levels of approximately 2000 and 12,000 mg/dl, the percentage "50,000 M.W. ApoA-1" was 20-25%. The ApoA-II contents of d smaller than 1.063 fractions were also increased in hyperlipidemia, but greater than 95% of ApoA-II was found in the HDL fractions in both normal and hyperlipidemic plasma both by column chromatography and ultracentrifugation. Thus, the molecular association of ApoA-I appears to be altered in hyperlipidemia.
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PMID:Plasma, apolipoprotein, A-I and A-II levels in hyperlipidemia. 22 Apr 91


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