Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Hyperlipidemia is associated with gram-negative sepsis. In this study we characterized the plasma lipoproteins of fasted and fed septic and control rats with respect to their lipid and apolipoprotein composition. Sepsis was induced by i.v. injection of 8 x 10(7) live Escherichia coli colonies/100 g body wt. Food was removed from fasted control and fasted E. coli-treated rats after injection. Fed rats were infused intragastrically with a nutritionally complete diet for 5 days prior to E. coli treatment. 24 h after treatment with E. coli, lipid and protein concentrations of very-low-density lipoprotein (VLDL) were over 2-fold higher in the fasted E. coli-treated rats than those of the fasted control rats. This appears to be due to a decrease in the clearance of VLDL. The relative composition of apolipoprotein B-48 and apolipoprotein E were lower while that of apolipoprotein B-100 was higher in fasted E. coli-treated rats than in fasted controls. Low-density lipoprotein (LDL) and high-density lipoprotein lipids were also significantly elevated, indicating greater synthesis of these particles during sepsis and food deprivation. By contrast, VLDL-triacyglycerol from fed, E. coli-treated did not differ from that of their respective controls although the total cholesterol remained elevated. Percentages of apolipoprotein B-48 and apolipoprotein B-100 increased while apolipoprotein E contributed significantly less to the total protein of VLDL from the E. coli-treated rats compared with controls. LDL lipids were also increased. In conclusion, gram-negative sepsis leads to marked changes in the plasma lipoprotein composition which may be attributed to altered hepatic synthesis, peripheral metabolism or hepatic uptake of lipoproteins and their remnants. These in turn may be a function of the nutritional status.
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PMID:Disturbances in the composition of plasma lipoproteins during gram-negative sepsis in the rat. 157 63

We studied a 39-year-old man who had palmar xanthomas complicated with marked hyperlipidemia. His serum cholesterol and triglyceride were 2000 and 6300 mg/dl, respectively. Serum apolipoprotein E (apo E) was undetectable in the patient by the methods of single radial immunodiffusion, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and radioimmunoassay. Serum apo E concentrations of his father and sister were low. This evidence is consistent with a diagnosis of familial apo E deficiency. We studied the synthesis of apo E in cultures of peripheral blood monocyte macrophages (M-M cultures) obtained from the patient, and detected no secretion of apo E in the culture medium and no newly synthesized apo E in the cell lysate. There were only trace amounts of apo E mRNA of the M-M cultures and the size of the mRNA appeared the same as normal apo E mRNA, indicating a different mutation of the gene from that of the case reported by Zannis et al. (J. Biol. Chem., 260 (1985) 12891).
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PMID:Apolipoprotein E deficiency with a depressed mRNA of normal size. 187 6

The effects of the nephrotic syndrome in rats on the cholesterol content and the biosynthesis of apolipoprotein E (apoE) by resident peritoneal macrophages have been investigated. Since the nephrotic syndrome has been associated with an increased risk of coronary atherosclerosis, we hypothesized that macrophages from nephrotic rats would accumulate cholesterol and undergo transformation into foam cells, with a concomitant increase in apoE biosynthesis. The nephrotic syndrome was induced in rats with puromycin aminonucleoside. Peritoneal macrophages exposed in vivo for 7-21 d to ascites fluid derived from plasma containing sixfold elevations of lipoproteins did not accumulate unesterified or esterified cholesterol. Nevertheless, immunoprecipitation assays after incubation of the isolated cells with [35S]methionine, or immunoblot analysis of the incubation medium demonstrated a 2.6-fold increase in apoE secretion compared with normal macrophages. This increase was accompanied by 5- to 10-fold increases in cellular apoE messenger RNA as determined by quantitative solution hybridization assay. Peritoneal macrophages cultured from nephrotic rats during the period of hypercholesterolemia also showed distinct and highly reproducible morphologic changes. The dissociation between apoE biosynthesis and macrophage cholesterol content provides new insight into the response of peritoneal macrophages in vivo to endogenous hyperlipemia.
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PMID:Macrophages from nephrotic rats regulate apolipoprotein E biosynthesis and cholesterol content independently. 199 33

Bile acid kinetics and biliary lipid composition were determined in seven subjects with primary dysbetalipoproteinaemia. They were all homozygous for the apolipoprotein E isoform E-2 and six of them were hyperlipidaemic (type III hyperlipoproteinaemia). With or without hyperlipidaemia, the apo E-2/2 phenotype was associated with increased bile acid formation (mean increase compared with 32 normolipidaemic controls, 43%; P less than 0.025). The biliary lipid composition was not different from that seen in the controls. The results indicate that the uptake by the liver of apo E-containing remnant particles is of importance for the regulation of hepatic cholesterol metabolism in man. It is suggested that hepatic cholesterol synthesis is stimulated in dysbetalipoproteinaemia, and that this leads to a compensatory increase in bile acid synthesis.
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PMID:Bile acid metabolism in familial dysbetalipoproteinaemia: studies in subjects with the apolipoprotein E-2/2 phenotype. 211 78

We have previously demonstrated an apolipoprotein E (apo E) mutant, apo E5, associated with hyperlipidemia and atherosclerotic vascular diseases. To investigate the possible mechanism of apo E5 involvement in the development of hyperlipidemia, we have isolated the apo E isoprotein and determined its binding activity to LDL (low density lipoprotein) receptors. It was shown that the apo E5 isoprotein was two times more active for binding to LDL receptors than apo E3. The concentration of apo E, at which 50% of 125I-labeled LDL bound to the receptor was displaced, was 29 ng/ml for apo E5 and 63 ng/ml for apo E3. This result suggests that the high affinity of apo E5 to LDL receptors results in a high uptake of apo E5-containing lipoproteins by the liver and leads to a down-regulation of LDL receptors in the liver. We can postulate that individuals with apo E5 are susceptible to hypercholesterolemia and in consequence to atherosclerosis.
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PMID:Enhanced binding activity of an apolipoprotein E mutant, APO E5, to LDL receptors on human fibroblasts. 233 12

The relationship between apolipoprotein E (Apo E) phenotypes and progression of coronary atherosclerosis was investigated in 125 patients with coronary artery disease (CAD) proven angiographically (101 males, 24 females). To elucidate the pure effect of Apo E phenotypes on lipoproteins and coronary atherosclerosis, patients with familial hypercholesterolemia were excluded from the subjects. As a control group, 129 normal healthy volunteers (84 males, 45 females) were studied. In the CAD group, VLDL and LDL levels increased and HDL level decreased regardless of Apo E phenotypes in both sexes. The incidence of E4 was higher and that of E2 was slightly lower in the CAD group than in the control group. Two patients with E5/3 who had high LDL-cholesterol levels were found in the male CAD group. LDL-cholesterol level in E3/2 was lower than in E4/3 and E3/3 in the male CAD group. VLDL-cholesterol/triglyceride and VLDL cholesterol/phospholipid ratios in E3/2 were significantly higher than in E4/3 and E3/3 in the male CAD group, but the difference was not so marked as found in typical type III hyperlipidemia. When the male patients with effort angina were examined, coronary score (index of the severity of CAD) was the lowest in E3/2. In addition, the mean age at the onset of CAD was significantly higher in E3/2 than in E4/3. In conclusion, E2 acts protectively against coronary atherosclerosis, while E4 promotes it through the modulation of LDL-cholesterol level.
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PMID:Apolipoprotein E phenotypes in patients with coronary artery disease. 235 52

The frequencies of the major apolipoprotein E(apo E) phenotypes in 65 normal, 426 hyperlipidemics, and 92 familial hypercholesterolemic Japanese subjects (FH) were studied, and features of hyperlipidemia compared between non-FH hyperlipidemia and FH. The frequencies of apo E phenotypes 3/3, 4/3, 3/2, 4/4 were almost the same in normal, non-FH hyperlipidemic, and FH subjects. The incidence of apo E7 was about 0.5% of total subjects. In type IV and V hyperlipidemias, incidence of E4/3 was higher than in any other hyperlipidemia. Incidence of E3/2 was also high in types III and V. In type II non-FH hyperlipidemia, incidence of E3/2 in type IIb was higher than in type IIa. VLDL-triglyceride, VLDL-cholesterol, apo C-II, apo C-III, and apo E levels were higher in E3/2 than in E3/3. But, in type IIa FH and type IIb FH, the incidence of E3/2 was the same, and lipid and apolipoprotein levels between 3/2 and 3/3 in FH were the same. These results indicate that allele epsilon 2 may be involved in the retention of VLDL or IDL, but not in FH.
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PMID:Frequency and role of apo E phenotype in familial hypercholesterolemia and non-familial hyperlipidemia in the Japanese. 237 85

Hyperlipidaemia and in particular hypercholesterolaemia is the best established cause of atherosclerosis. As awareness of this association grows amongst a more informed populace, there will be an increasing demand for plasma lipid screening. The traditional measurements of total plasma cholesterol and triglycerides for the assessment of hyperlipidaemia and its attendant CHD risk are now augmented by the availability of routine methods for separating and quantitating the different plasma lipoproteins, thus vastly improving diagnostic sensitivity. Because it is the major carrier of cholesterol in plasma and because the mechanistic evidence relating it to atherogenesis is strongest, elevated levels of the low density lipoproteins (LDL) are undesirable: high levels of high density lipoproteins (HDL), on the other hand, decrease the risk. Currently, plasma LDL and HDL concentrations are most frequently assessed by measuring their cholesterol content. However, the measurement of apolipoproteins, the protein components of the lipoproteins, may yet prove to be superior in predictive value, though they can hardly be expected to replace the older tests as first line screening tests by virtue of their relative costs and sophistication in terms of instrumentation and techniques. Additional diagnostic tests have been developed and newer ones will no doubt continue to evolve with further technical advancements and a better understanding of the pathogenesis of atheromas and vessel disease. The current lineup includes HDL subfractions, unique lipoproteins such as Lp(a) and beta-migrating VLDL and apolipoprotein E variants.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma lipid profiles: the expanding repertoire of tests, their clinical significance and pitfalls. 267 44

The uptake and transport of beta-VLDL by the aortic endothelium was investigated in normal and hyperlipidemic rabbits fed a cholesterol-enriched diet for 1 week to 5 months. Weekly (in the first month) or every other week afterwards, animals were given one of the following probes: (a) [125I]-beta-VLDL injected in vivo and after 24 h the whole aorta or its intima and media were separately collected and examined by spectrometry and autoradiography; (b) [125I]-beta-VLDL coupled to the fluorescent probe 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate perfused in situ for 1-2 h and aorta examined by radioassay and fluorescence microscopy; (c) beta-VLDL-gold complex perfused in situ for 10-15 min and aortic fragments examined by electron microscopy. In addition, cryosections of aortic wall were processed for the immunocytochemical detection of apolipoprotein B and apolipoprotein E. The results showed that both in normal and hyperlipidemic rabbits, the aortic endothelium transports plasma beta-VLDL by a dual pathway: (i) endocytosis involving coated pits and vesicles, endosomes, multivesicular bodies and lysosomes, and (ii) transcytosis, the predominant process, carried out by plasmalemmal vesicles. Both processes, and especially transcytosis, are markedly increased in hyperlipidemia leading to progressive accumulation of beta-VLDL or/and its components in the subendothelial extracellular matrix. In prelesional stages of atherogenesis, beta-VLDL-gold complexes or deposits of apo B and apo E were detected in close association with extracellular liposomes. With the appearance of intimal macrophage-derived foam cells, the immunoperoxidase reaction product, revealing the presence of the two apolipoproteins, could also be seen in intracellular lipid inclusions.
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PMID:Transport pathways of beta-VLDL by aortic endothelium of normal and hypercholesterolemic rabbits. 271 64


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