Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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

Circulating lipid levels and lipoprotein patterns in the Syrian hamster were determined at various times after subcutaneous inoculation with simian virus 40 (SV40) strain F, strain A-2895, or Fortner melanoma tumor cells. SV40 F tumors induced a rapid triphasic elevation of serum total lipids through inhibition of prebeta lipoprotein catabolism. Alpha lipoprotein levels declined in proportion to tumor mass. Liver wet weight and total lipid content increased significantly, but a normal rate of 3H-glycerol incorporation into polyanion precipitable (prebeta) serum lipoprotein was maintained. Determination of serum endogenous lipase, lecithin:cholesterol acyltransferase (LCAT), and cholinesterase activities indicated that these enzymes were not primarily responsible for the tumor-induced hyperlipidemia. Tumor-bearing animals also had selectively increased rates of protein and lipid excretion into the urine, with no evidence of gross hepatocellular or kidney damage. Growth of SV40 A-2895 tumors in hamsters resulted in a large increase in the rate of prebeta lipoprotein synthesis and degradation. Circulating prebeta lipoprotein levels were elevated much later in these animals, subsequent to a marked decrease in LCAT activity. Quite different results were obtained with Fortner melanoma, even large tumors having only a moderate effect on serum total lipid levels and lipoprotein patterns in the Syrian hamster.
...
PMID:Effect of simian virus 40 subcutaneous tumors on circulating lipids and lipoproteins in the Syrian hamster. 16 32

Plasma lecithin:cholesterol acyltransferase (LCAT) activity is increased during the clearance phase of alimentary lipemia induced by a high-fat test meal in normal subjects. Ultracentrifugal fractionation of high density lipoproteins (HDL) into HDL(2), HDL(3), and very high density (VHD) subfractions followed by analyses of lipid and protein components has been accomplished at intervals during alimentary lipemia to seek associations with enzyme changes. HDL(2) lipids and protein increased substantially, characterized primarily by enrichment with lecithin. HDL(3), which contain the main LCAT substrates, revealed increased triglycerides and generally reduced cholesteryl esters which were reciprocally correlated, demonstrating a phenomenon previously observed in vitro by others. Both changes correlated with LCAT activation, but partial correlation analysis indicated that ester content is primarily related to triglycerides rather than LCAT activity. The VHD cholesteryl esters and lysolecithin were also reduced. Plasma incubation experiments with inactivated LCAT showed that alimentary lipemic very low density lipoproteins (VLDL) could reduce levels of cholesteryl esters in HDL by a nonenzymatic mechanism. In vitro substitution of lipemic VLDL for postabsorptive VLDL resulted in enhanced reduction of cholesteryl esters in HDL(3) and VDH, but not in HDL(2), during incubation. Nevertheless, augmentation of LCAT activity did not result, indicating that cholesteryl ester removal from substrate lipoproteins is an unlikely explanation for activation. Since VHD and HDL(3), which contain the most active LCAT substrates, were also most clearly involved in transfers of esters to VLDL and low density lipoproteins, the suggestion that LCAT product lipoproteins are preferentially involved in nonenzymatic transfer and exchange is made. The main determinant of ester transfer, however, appears to be the level of VLDL, both in vitro and in vivo. Rose, H. G., and J. Juliano. Regulation of plasma lecithin: cholesteryl acyltransferase in man. III. Role of high density lipoprotein cholesteryl esters in the activating effect of a high-fat test meal.
...
PMID:Regulation of plasma lecithin:cholesterol acyltransferase in man. III. Role of high density lipoprotein cholesteryl esters in the activating effect of a high-fat test meal. 22 5

Vitamin E deficiency in two species of monkeys (capuchins and cynamolgus) reduced the in vitro cholesterol esterification by plasma lecithin-cholesterol acyltransferase. The reduction was greates in the most deficient species and in animals fed a diet rich in polyunsaturated fat (safflower oil) stripped of vitamin E. The best correlate of total esterification was the plasma concentration of free cholesterol which reflected the degree of hyperlipidemia, found to be greatest in capuchins fed coconut oil. A logical explanation for the decreased LCAT activity in vitamin E deficiency would be peroxidative damage of substrate (the PUFA of lecithin) or of sulfhydryl sited on lecithin-cholesterol acyltransferase itself. However, neither case was fully supported by the data suggesting that additional information concerning the nature of the reaction and the role of vitamin E is required.
...
PMID:Depression of lecithin-cholesterol acyltransferase esterification in vitamin E-deficient monkeys. 80 56

The present study demonstrates very high levels of plasma lipids and high density lipoprotein (HDL) apolipoproteins (apoA-I and apoE) in female Nagase analbuminemic rats (NAR) fed a semi-synthetic diet in order to further increase the hyperlipidemia present in this strain. Plasma apoB-containing lipoproteins (very low, intermediate, and low density lipoproteins) were also elevated in NAR. Plasma cholesterol was mainly present in lipoprotein particles with a density between 1.02 and 1.12 g/ml. Separation of lipoprotein classes by gel filtration showed that the major cholesterol-carrying lipoprotein fractions in NAR plasma are apoE-rich HDL and apoA-I-rich HDL. The high HDL levels in NAR are explained, at least partly, by the two- to threefold elevated activity of plasma lecithin:cholesterol acyltransferase (LCAT). The lysophosphatidylcholine generated in the LCAT reaction, as well as plasma free fatty acids, are bound to lipoproteins in NAR plasma. A study was carried out to determine whether the elevated LDL and aopoE-rich HDL levels could be corrected by administration of the HMG-CoA reductase inhibitor pravastatin (at a dose of 1 mg/kg per day). Pravastatin treatment results in a 43% decrease in plasma triglycerides in NAR, but not in Sprague-Dawley (SDR) rats, and had no significant effect on plasma total cholesterol, phospholipids apolipoproteins A-I, A-IV, B, or E, as well as on plasma LCAT activity levels in NAR or SDR.
...
PMID:Hyperlipoproteinemia in Nagase analbuminemic rats: effects of pravastatin on plasma (apo)lipoproteins and lecithin:cholesterol acyltransferase activity. 177 Feb 92

Previous observations demonstrated that steroid hormones associate with plasma lipoproteins. The objective of this study was to estimate the relative importance of lipoproteins as steroid hormone binding agents in comparison to sex hormone binding globulin, corticosteroid binding globulin, and albumin in both normal and hyperlipidemic human plasma. The 16 steroid hormones and related metabolites included in the study were: androstanediol, androstenediol, androstenedione, androsterone, corticosterone, cortisol, dehydroepiandrosterone, deoxycorticosterone, dihydrotestosterone, estradiol, estriol, estrone, 17 alpha-hydroxyprogesterone, pregnenolone, progesterone, and testosterone. The binding activity of these 16 steroid hormones with purified high density lipoprotein (HDL), low density lipoprotein and very low density lipoprotein were separately evaluated by equilibrium dialysis incubations to yield 48 steroid hormone-lipoprotein combinations for further study. In incubations with HDL, six steroid hormones (androstenediol, dehydroepiandrosterone, dihydrotestosterone, estradiol, pregnenolone, and progesterone) were identified as non-equilibrium, apparently due to metabolic conversion of the steroid hormones. The metabolic activity for the three delta 5-3 beta hydroxy steroids and estradiol appears to be fatty acid esterification by lecithin:cholesterol acyltransferase. The computer program TRANSPORT, which was used to evaluate only the nonspecific steroid hormone-lipoprotein association levels in a 16 x 6 matrix at simultaneous equilibrium, indicated that lipoprotein-bound steroid hormones ranged from 1% for cortisol to 56% for pregnenolone in normal human blood. Simulated projections of the increase in nonspecific steroid hormone association with lipoproteins during hyperlipidemia are also presented. These results demonstrate how lipoproteins are likely to be important in the transport and metabolism of steroid hormones in human plasma.
...
PMID:Nonspecific and metabolic interactions between steroid hormones and human plasma lipoproteins. 228 Jun 75

Hyperlipidemia is a common complication of PBC. Ten patients with serologically and histologically defined PBC were randomized to receive either oral cyclosporin A (CyA) or placebo for one year. Fasting blood samples were obtained from subjects at the beginning, and following one year of treatment, for plasma lipids, apolipoproteins AI (apo AI) and B (apo B), and lecithin-cholesterol acyltransferase (LCAT) activity. On entry to the study there were no significant differences between groups for serum concentrations of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), free cholesterol (FC), total phospholipids (TPL), apo AI, apo B and LCAT activity. Compared to normal laboratory values, baseline TC was elevated in 5/10, LDL-C in 5/10, TPL in 6/10, while LCAT activity was decreased in 8/10 patients. The percent change after one year for CyA group vs the placebo group are as follows: total cholesterol, -22 vs -8%; LDL cholesterol -33 vs -25%; free cholesterol, -39 vs -14%; total phospholipids, -46 vs -23%; and LCAT activity, +/- 236 vs +/- 43%. The decrease in TC, LDL-C, FC, TPL with increase in LCAT activity suggests that CyA administration is associated with improvement in the lipid abnormalities of PBC.
...
PMID:Effect of cyclosporin A on serum lipids in primary biliary cirrhosis patients. 261 91

Plasma lipid abnormalities derive their importance from their association with coronary artery disease. Elevated cholesterol levels accentuate risk, and clinical trials have shown that reductions lead to a decline in coronary events. The major plasma lipids, cholesterol and triglyceride, circulate in association with specific proteins as lipid-protein or lipoprotein complexes. The proteins direct and regulate the metabolism of these complexes by interacting with tissue enzymes and receptors. The metabolic fate of circulating triglyceride is governed by the activity of the enzyme lipoprotein lipase, situated in adipose tissue and skeletal muscle. Cellular demand for cholesterol, on the other hand, is met by activation of a specific receptor which mediates the delivery of sterol-rich lipoproteins to lysosomal degradation in liver and peripheral tissues. In order to prevent excess cholesterol accumulation at the periphery, there is a system of reverse cholesterol transport which involves assimilation and trapping of the sterol in the plasma lipoproteins through the action of the enzyme lecithin:cholesterol acyltransferase. Thereafter, the cholesterol is delivered to the liver, the only organ capable of excreting it in significant amounts. Disturbances in these processes may produce gross changes in the plasma lipid profile, clearly recognizable as hyperlipidaemia. However, it is becoming increasingly clear that a number of inherited traits can subtly perturb the lipoprotein spectrum and increase coronary risk even in subjects whose plasma lipoprotein profile would be considered normal.
...
PMID:Lipid transport through the plasma: the metabolic basis of hyperlipidaemia. 333 Apr 20

Plasma lipoproteins of d<1.006 g/ml, d 1.006-1.019 g/ml, and d 1.019-1.063 g/ml from patients with familial lecithin:cholesterol acyltransferase deficiency yielded abnormal subfractions upon being separately filtered through 2% agarose gel. A subfraction that emerged with the void volume and contained unusually large amounts of unesterified cholesterol and phosphatidylcholine was present in each lipoprotein group, and in each group this subfraction was less prominent in the nonlipemic plasma of one patient than in the lipemic plasma of other patients. A subfraction containing smaller lipoproteins also was present in each lipoprotein group. These lipoproteins were of the same size as normal lipoproteins of the corresponding density, but contained abnormally small amounts of cholesteryl ester. The lipoproteins of 1.019-1.063 g/ml contained abnormal components of intermediate molecular weight as well as large and small abnormal components similar to those described previously. The intermediate components were more prominent in the nonlipemic plasma but were easily recognized in the hyperlipemic plasma as a peak of S(f) 20-30 in the analytical ultracentrifuge. Also they could be recognized, upon electron microscopy of the lipoproteins of d 1.019-1.063 g/ml, as particles 340-1000 A in diameter. The data suggest that related large, abnormal particles pervade the patients' very low and low density lipoproteins, and that the large particles are affected by, but are not dependent on, the lipemia that frequently accompanies the disease. The smaller very low and low density lipoproteins appear to be counterparts of lipoproteins present in normal plasma. Their abnormal composition is compatible with the possibility that lecithin:cholesterol acyltransferase normally decreases the triglyceride and phosphatidylcholine and increases the cholesteryl ester of very low density and low density plasma lipoproteins in vivo.
...
PMID:Plasma lipoproteins in familial lecithin: cholesterol acyltransferase deficiency. Further studies of very low and low density lipoprotein abnormalities. 434 84

We have studied the effect of long-term hyperlipemia and atherosclerosis in squirrel monkeys on the metabolism of lysolecithin-(14)C (1-palmitoyl-1'-(14)C sn-glycerol 3-phosphorylcholine) in order to explain elevated plasma and arterial concentrations of lysolecithin. The die-away curves of lysolecithin-(14)C from plasma and the timing of appearances of other (14)C-labeled moieties in plasma and other tissues demonstrated a complex pattern of metabolic reactions. There was a rapid equilibration of specific activities of lysolecithin of plasma, liver, and aortic intima plus inner media. The specific activities of lecithin peaked first in liver, then in plasma, and rose slowly in aortic intima plus inner media. The appearance of lecithin-(14)C in heart and skeletal muscle was also slower than in the liver and some other tissues. Triglycerides, and to a lesser extent, cholesteryl esters contained radioactivity. The concentrations of aortic lysolecithin in the atherosclerotic aortas were several times greater than comparable values for control aortas, and the time of equilibration of plasma and aorta lysolecithin-(14)C was much greater for the atherosclerotic group. The quantities of lysolecithin in plasma and in the pool of which the plasma was a part, were increased with hyperlipemia and atherosclerosis, as was the rate of lysolecithin production in the fast pool. Hyperlipemia was also associated with an early increase in plasma lecithin:cholesterol acyltransferase (LCAT) activity in vitro. Furthermore, nutritional hyperlipemia influenced the distribution of lysolecithin-(14)C and lecithin-(14)C between different plasma lipoproteins. The increase in concentrations of lysolecithin in the aorta occurred more slowly than that in plasma after we had induced hyperlipemia in the monkeys.
...
PMID:Metabolism of lysolecithin in vivo: effects of hyperlipemia and atherosclerosis in squirrel monkeys. 499 21

Serum lipids, apoprotein and lecithin-cholesterol acyltransferase activities were studied in 27 renal transplant recipients with stable and normal renal function (serum creatinine 0.16 mM/l or less) sustained for more than 1 year following grafting. Hypertriglyceridemia, which was characteristic of hyperlipidemia in 18 hemodialyzed patients with chronic renal failure, was no longer manifest in transplant recipients. On the other hand, de novo hypercholesterolemia was observed posttransplant with mean serum levels of 5.82 +/- 1.34 versus 5.01 +/- 0.88 mM/l in 575 normal controls. As to the high-density lipoprotein metabolism, the cholesterol content (1.72 +/- 0.56 mM/l) was significantly higher in transplant patients than in hemodialyzed patients (0.82 +/- 0.31 mM/l). In contrast, no variation in apoprotein A-I levels was found between both groups of patients, which produced an elevated high-density lipoprotein cholesterol:apoprotein A-I ratio. Thus, derangement in the serum lipid profile, although qualitatively different, continued to be present following transplantation, and its relevance to the cardiovascular morbidity in these patients remains to be evaluated.
...
PMID:De novo development of hypercholesterolemia and elevated high-density lipoprotein cholesterol: apoprotein A-I ratio in patients with chronic renal failure following kidney transplantation. 641 53


1 2 3 4 Next >>

---