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)

The mechanism leading to hyperlipidemia in the nephrotic syndrome is not fully understood but may be related in part to loss of high density lipoproteins in the urine of patients with nephrosis. To prove this hypothesis, we compared serum lipoprotein profiles with the excretion of high density lipoproteins in urine in 19 nephrotic patients. Serum cholesterol ranged from 19-152 (median value 45) mg/dl in very low density lipoproteins (VLDL), from 130-443 (median 186) mg/dl in low density lipoproteins (LDL) and from 19-64 (median 33) mg/dl in high density lipoproteins (HDL). Hyperlipoproteinemia was found in 17 patients, which was classified as phenotype IIa (Fredrickson) in 2, as phenotype IIb in 9 and as phenotype IV in 6 subjects. Two patients showed normal lipoprotein patterns. VLDL- and LDL-cholesterol were not found in detectable amounts in urine, whereas HDL-cholesterol was measured in low concentrations from 0.1-8.3 mg/24 h in all samples. There was no correlation between serum HDL-cholesterol and urinary HDL-cholesterol, but a positive correlation between serum LDL-cholesterol and urinary HDL-cholesterol (r = +0.54, p less than 0.05). However, the total amount of the daily urinary loss of HDL (less than 1% of total plasma HDL) seems not to be sufficient to explain hyperlipoproteinemia in the nephrotic syndrome.
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PMID:Relation of hyperlipidemia in serum and loss of high density lipoproteins in urine in the nephrotic syndrome. 367 14

The viscosity of the extracellular medium of cultured hepatocytes has been shown to be a regulator of the secretion and synthesis of very low-density lipoproteins (Yedgar et al., J. Biol. Chem. 257: 2188-2192, 1982). At present, the role of plasma viscosity in regulation of plasma lipoprotein levels was examined in vivo using nephrotic hyperlipidemic rats. Plasma viscosity was increased by injection of macromolecules: simultaneously with induction of nephrosis by aminonucleoside; and after the lipid level had reached its maximum. In experiment 1 the elevation of plasma viscosity (which persisted for at least 2 days) delayed the development of the hyperlipidemia by at least 2 days. In experiment 2 increasing the plasma viscosity reduced plasma triglyceride and cholesterol levels by 70 and 40%, respectively, within 2 days. The hyperlipidemia was accompanied by increased plasma viscosity. The contribution of lipoproteins to plasma viscosity was 27% in the nephrotic-hyperlipidemic rats, compared with 4% in normal rats. It is suggested that plasma viscosity regulates lipoprotein levels in vivo concordant with the observation in cultured hepatocytes.
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PMID:Regulation of plasma lipid levels by plasma viscosity in nephrotic rats. 396 45

Adriamycin, an anticancer drug, caused dramatic increases in the serum lipid levels of rats fed a high-cholesterol diet. Male Lewis inbred rats were fed a basal or 1.5% cholesterol diet containing 0.5% cholic acid for 8 weeks. The rats were injected with adriamycin in doses of 1.5 mg/kg body weight, twice a week, and 6.0 mg/kg body weight, every other week. The serum lipid peroxide level gradually rose in adriamycin-treated rats, reaching a four-fold level at the end of the experiment. Cholesterol feeding, however, had a lowering effect on the lipid peroxide level. Adriamycin treatment or cholesterol feeding moderately elevated serum lipid levels, but their combination exerted a synergistic effect. In rats injected with a large dose of adriamycin and fed a high-cholesterol diet, the serum cholesterol, triglyceride and phospholipid levels strikingly increased by approx. 2000, 1500 and 1300 mg/100 ml, respectively. However, the ester ratio of cholesterol remained almost constant. Furthermore, serum GOT, GPT and ALP activities were only slightly different from the control values. Adriamycin treatment produced severe hypoalbuminemia. Ascites was also observed in rats given a large dose of adriamycin. The present findings indicate that the hyperlipidemia we observed may basically result from adriamycin-induced nephrosis and can be markedly enhanced when rats are fed a high-cholesterol diet. In spite of remarkably high levels of serum lipids and lipid peroxides, the aortic cholesterol level increased only slightly.
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PMID:Hyperlipidemic effects of adriamycin in rats. 409 81

Factors involved in the hyperlipidemia of nephrosis have been studied in seven patients. The turnover of triglyceride was measured in plasma very low density lipoproteins after the injection of glycerol-(14)C. The turnover of esterified cholesterol was measured in whole plasma and in very low density lipoproteins after the injection of mevalonic acid-2-(3)H. Urine protein loss was found to be significantly correlated with the plasma concentrations of triglyceride and free cholesterol, suggesting that increasing loss of protein is associated with the formation of larger lipoproteins. Lactescent plasmas were found in the subjects with the greatest protein loss. The turnover rate of triglyceride tended to be higher among subjects with higher than with lower triglyceride concentrations and was on the average higher than among six normotriglyceridemic subjects. However, there was also evidence for decreased clearance of glyceride from plasma. The hypertriglyceridemia of nephrosis appeared to reflect both increased formation of glyceride and decreased removal of glyceride from plasma. The turnover of esterified cholesterol was significantly higher in whole plasma of nephrotic subjects than in normocholesterolemic nonnephrotic patients. Esterified cholesterol turnover in very low density lipoproteins was raised in the two subjects in whom a major part of total esterified cholesterol was carried in this lipoprotein fraction. These studies were repeated in one subject after remission was induced. The cessation of urinary loss of protein was associated with reductions in the concentrations and turnover of triglyceride and esterified cholesterol. The increased turnover of plasma lipids in nephrosis may reflect the general increase in the formation of protein.
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PMID:Studies on the turnover of triglyceride and esterified cholesterol in subjects with the nephrotic syndrome. 565 95

Chronic renal disease with secondary hyperlipidemia is highly atherogenic. In uremia and patients on chronic hemodialysis there is a high incidence of atherosclerotic complications whereas the incidence of atherosclerotic disease is relatively low in the nephrotic syndrome. This is surprising, as nephrosis produces type-II hyperlipidemia, which is usually highly atherogenic. In this study 10 patients (5 male, 5 female) with a newly diagnosed nephrotic syndrome were compared to 10 controls (5 male, 5 female). As laboratory parameters, lipids, lipoproteins (VLDL, IDL, LDL, HDL2 and HDL3 by rate zonal centrifugation) and the percentage composition of the major apolipoproteins in VLDL, HDL2 and HDL3, as well as lipoprotein lipase (LPL), hepatic lipase (HTGL) and lecithin-cholesterol-acyl-transferase (LCAT) were measured. In nephrotic patients significantly higher plasma levels of cholesterol, triglycerides, phospholipids, VLDL, IDL and LDL were found, whereas HDL-chol, HDL2 and HDL3 were unchanged. LPL and HTGL were both significantly impaired, whereas LCAT was distinctly increased. The percentage composition of apolipoproteins in HDL2 and HDL3 was normal. In nephrotic VLDL, apo-AI was distinctly increased at the expense of a decrease in apo-CII, and increased LCAT was explained by the relative rise of apo-AI in nephrotic VLDL. The increase in apo-AI in VLDL is discussed as a possible reason for the low atherogenic risk of secondary hyperlipidemia in nephrotic syndrome.
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PMID:[Lipoproteins, apolipoproteins, lipoprotein lipase, hepatic triglyceride lipase and lecithin cholesterol acyltransferase in patients with nephrotic syndrome]. 661 72

Several enzyme activities involved in lipid hydrolysis (acid and neutral cholesterol esterase and lipase) or synthesis (acyl-CoA synthetase, acyl-CoA: cholesterol acyltransferase and cholinephosphotransferase) were assayed in the aortas of rats with nephrosis induced by daunomycin and of rats fed on high cholesterol diet. In nephrotic rats activities of some enzymes involved in lipid hydrolysis, but not in synthesis, were increased. On the contrary, in rats fed on high cholesterol diet, the activities of all enzymes involved in lipid synthesis were significantly increased, with some increase in those involved in lipid hydrolysis. In nephrotic rats fed on high cholesterol diet all enzyme activities were markedly increased. From the view point of accumulation of cholesterol ester (CE), the ratio of hydrolysis of CE in lysosomes to CE incorporated from the blood and the ratio of hydrolysis of CE to reesterification of free cholesterol in microsomes were considered to be important. From this point of view, nephrotic hyperlipidemia was not so atherogenic as hyperlipidemia induced by the diet. The role of serum high density lipoproteins in lipid metabolism in the aorta was discussed.
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PMID:Lipid metabolism in the aorta of daunomycin-induced nephrotic rats. 664 60

Clinical manifestations and immunological characteristics in a series of 15 patients with systemic lupus erythematosus and renal involvement are presented. These findings have been correlated to different pathologic lesions and compared to another series of patients without renal involvement. The overall rate of renal involvement was 25 percent, with ages ranging from 14 to 47 years. A female predominance was noticed. Histopathologic findings were as follows: focal glomerulonephritis (five cases), and minimal changes (one case). Under a histological glomerulonephritis (two cases); membranous glomerulonephritis (one case), and minimal change (one case). Under a histological standpoint the earliest lesions had the worse prognosis. Patients with diffuse glomerulonephritis showed a high degree of renal function impairment. Urinary infection was present in half of the cases. A significant hyperlipidemia was found in patients with nephrosis. Proteinuria and abnormal urinary sediment were common findings in all histologic types. Antinuclear antibodies, were positive in 14 cases, with statistical significant high titres in diffuse glomerulonephritis. Serum immunoglobulins IgG and IgA were elevated. Decrease of serum complement levels (C3, C4, C3PA and C5) were found in patients with renal involvement.
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PMID:[The spectrum of lupus nephropathy]. 742 56

Although lipoprotein abnormalities of the nephrotic syndrome are assumed to be related to the presence of proteinuria, this topic has not been investigated extensively. We measured lipoproteins from 19 nonuremic patients during and after remission of the nephrotic syndrome in an effort to determine the extent of their putative atherogenicity. As expected, disturbances involved primarily the apoprotein B-containing lipoproteins. No patient showed serum lipoprotein(a) [Lp(a)] < 300 mg/L during the acute phase. Lp(a) concentrations correlated significantly with those of apoprotein B, and both values decreased dramatically with the remission of the nephrotic syndrome. Surprisingly, despite the resolution of proteinuria, concentrations of intermediate-density lipoproteins and Lp(a) remained above normal in hypertriglyceridemic patients, suggesting a residual effect of nephrosis in the overall lipoprotein transport. Accumulation of atherogenic remnants should be considered a characteristic of the hyperlipidemia of the nephrotic syndrome, and aggressive treatment to reduce proteinuria is mandatory.
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PMID:Accumulation of atherogenic remnants and lipoprotein(a) in the nephrotic syndrome: relation to remission of proteinuria. 776 11

Hyperlipidemia and lipoprotein abnormalities are often encountered in patients with nephrotic syndrome or chronic renal disease and also in those undergoing haemodialysis and with renal transplant. Even though the significance of lipid deposition in renal tissue and the role of lipoproteins in the pathogenesis of renal disease in man is unclear, experimental and clinical data indicate a possible damaging effect of a disturbed lipid metabolism on the kidney. In humans, glomerular lipid deposition is observed in genetic diseases such as Fabry's disease, lecithin:cholesterol acyltransferase activity (LCAT) deficiency and arteriohepatic dysplasia, and in diseases with acquired disturbance of lipid metabolism such as nephrotic syndrome and cholestatic liver disease. Studies on animals with lupus nephritis, aminonucleoside nephrosis, reduced renal mass, diabetes mellitus or systemic hypertension have shown that cholesterol can increase the incidence of glomerulosclerosis. As most of these studies have been performed in the rat, which has a different lipoprotein profile to that of man, these results should be carefully interpreted with regard to their relevance for humans. In vitro cell culture studies on human glomerular cells have given some preliminary insights into the cellular mechanisms of lipid induced glomerular damage. Apo E-containing lipoproteins, which are pathologically elevated in many renal diseases, are avidly taken up by human mesangial cells. These cells seem to play a central role in the initiation of glomerulosclerosis by inducing proliferation and production of excess extracellular matrix. Lipoproteins are able to stimulate DNA synthesis in these cells, and increase the synthesis of mitogens and extracellular matrix protein. The pathogenic role of oxidized lipoproteins has not yet been defined. Human mesangial cells do not seem to take up these modified lipoproteins. However, macrophages infiltrate glomeruli and may constitute the stimulus for the generation of minimally modified lipoproteins and their cellular uptake. The data from animal experiments suggest that treatment that corrects hyperlipidemia may have an ameliorative effect on renal function. Thus, there are strong indications that lipoproteins may play a critical role in mediating the development of glomerulosclerosis.
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PMID:The role of lipids in nephrosclerosis and glomerulosclerosis. 794 52

The effects of fluvastatin, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on the hyperlipidemia associated with nephrosis were studied. Nephrotic rats, induced by a single intraperitoneal injection of puromycin aminonucleoside (100 mg/kg body weight), had significantly higher plasma triglyceride (TG), total cholesterol and apoprotein (apo) B concentrations than controls. Fluvastatin was administrated as a 0.01% solution in drinking water for 14 days to either normal control or nephrotic rats. Concentrations of TG and apo B in plasma, and very low-density lipoprotein (VLDL) in nephrosis were completely normalized by the treatment with fluvastatin, but concentrations of cholesterol in plasma and each lipoprotein fraction were not altered by the treatment. The ratio of apo E to C in VLDL was significantly decreased in nephrotic rats, but the fluvastatin treatment increased this ratio. TG secretion rate estimated by the Triton WR1339 method was significantly increased in nephrotic rats, but was normalized by fluvastatin. Percent composition of TG in newly secreted VLDL particles in post-Triton plasma was not decreased by fluvastatin treatment, suggesting that the number of newly secreted VLDL particles was reduced by the treatment. Postheparin plasma lipolytic activities were not affected by the fluvastatin treatment. These results demonstrate that fluvastatin can effectively ameliorate the high concentration of VLDL by suppressing the hepatic secretion in nephrotic rats, and suggest that an inhibition of cholesterol biosynthesis suppresses VLDL secretion from the liver.
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PMID:Fluvastatin, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, suppresses very low-density lipoprotein secretion in puromycin aminonucleoside-nephrotic rats. 807 13


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