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)

In experimental nephrosis, a decrease in plasma albumin resulting from proteinuria causes a decreased in the plasma oncotic pressure. The existence of an osmoreceptor, which responds to the low oncotic pressure and produces a factor(s) that signals the liver to increase the secretion of plasma proteins, is postulated. The hyperlipidemia characteristic of the nephrotic syndrome results primarily from increased hepatic secretion of apolipoproteins and lipoproteins representing the entire density spectrum from VLDL, IDL, and LDL to HDL. Not all plasma proteins and apolipoproteins are affected to the same extent. Increased mRNA levels due to increased transcription have been shown for albumin and apolipoprotein A-1 (apoA-1). The increased secretion of VLDL, the major vehicle for triglyceride transport from the liver, appears to be due mainly to posttranscriptional events possibly related to increased lipogenesis. Once proteinuria begins, the demand for amino acids for albumin and apolipoprotein synthesis by the liver is increased. To meet this demand, protein catabolism in the peripheral tissues is increased. One manifestation of this process is a decrease in lipoprotein lipase which reduces VLDL catabolism, contributing to the sustained elevation of plasma VLDL. The spectacular overproduction of apoA-1 in nephrosis in the rat is accompanied by a decreased fractional catabolic rate (FCR), contributing to the maintenance of high levels of HDL. Urinary loss of HDL and its renal catabolism does not account for the decreased FCR. The reason for the decreased FCR is not known. Work with nephrotic rats overexpressing transgenic human apoA-1 has shown that human A-1 forms smaller HDL3-sized particles, rather than the larger HDL2 of the rat. This may contribute to the failure of HDL levels to increase in the human nephrotic syndrome. High plasma VLDL and LDL with normal or low HDL probably account for the increased incidence of coronary artery disease in the nephrotic syndrome.
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PMID:Lipoprotein metabolism in experimental nephrosis. 893 62

Cardiovascular diseases remain to be the 4th rank of top ten causes of mortality in Taiwan in recent years. Atherosclerosis and coronary artery disease, which often culminating in the occurrence of myocardial infarction and congestive heart failure, are responsible for the majority of these death. One of the prominent features of atherosclerotic lesion is local accumulation of lipids, mainly in the forms of cholesteryl ester and free cholesterol, either within cells or extracellularly in matrix. Repeated endothelial injury and enhanced lipid infiltration are critical events in the development of atherosclerosis. Plasma lipoproteins may enter the arterial wall through endothelium, either transcellularly via vesicular transport or paracellularly via intercellular junction. Our previous studies have demonstrated that most of the arterial endothelial cells in mitosis are associated with the leakage of fluorescently labeled albumin and low density lipoproteins. Subsequently, such transendothelial leakage of macromolecules is also shown to be associated with endothelial cell death as assessed by immunocytochemical staining for IgG. These findings suggested that transiently leaky junctions occurring during endothelial cell turnover may provide potentially important pathways for increasing transport or leakage of macromolecules, including atherogenic LDL, across the vascular endothelium. Electron microscopic study using horseradish peroxidase as a tracer revealed markedly widening of intercellular junctions around endothelial cells in mitosis providing direct evidence in support of "cell turnover-leaky junction" theory for the localization of atherogenesis. Hypertension, smoking, diabetes, and hyperlipidemia are well-known major risk factors for atherosclerosis and coronary heart disease. In a series of investigations, we examined the hypothesis that hypertension smoking, diabetes, and hyperlipidemia increase the arterial endothelial cell turnover and hence transendothelial macromolecular transport, which may have some implications in increasing lipid entry and thus, accelerating atherogenesis. Animal experiments were performed in adult male spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) normotensive rats, and Sprague-Dawley (SD) rats. SHRs were used as hypertensive group with WKY rats as normotensive control. SD rats were given nicotine at a dose of 5 mg/Kg body wt/ day in their drinking water to mimic smoking effect over a period of 6 weeks. Diabetes was induced in SD rats by single intraperitoneal injection of 60 mg/Kg body wt of streptozotocin. The duration of diabetes was 6 weeks. Also, SD rats were fed a diet containing 5% cholesterol for 6 weeks to induce hyperlipidemia. Age-matched rats of comparable number served as control for each experimental group. In en face preparations of thoracic aorta, mitotic endothelial cells were identified by hematoxylin staining, immunoglobulin G-containing dying or dead endothelial cells were detected by an indirect immunoperoxidase method, and endothelial leakage to Evans blue-albumin (EBA) complexes (5 minutes after intravenous injection) was visualized and quantified by fluorescence microscopy. The results showed that SHR, chronic oral nicotine-treated rats, diabetic, rats, and hyperlipidemic rats, when compared to control rats, had higher values for the frequency of endothelial cell death and the number density of EBA leaky foci in the aorta. These findings suggested that hypertension, cigarette smoking, diabetes mellitus, and hyperlipidemia become risk factors in atherogenesis by increasing the rate of arterial endothelial cell turnover and the associated endothelial cell turnover and the to the consequent enhanced entry of atherogenic lipoproteins into the arterial wall and accelerated atherogenesis.
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PMID:Risk factors, endothelial cell turnover and lipid transport in atherogenesis. 903 45

A rapid and reliable method for measuring serum albumin employing bromcresol green is described. The addition of albumin to a solution of bromcresol green in a 0.075 M succinate buffer pH 4.20 results in an increase in absorbance at 628 nm. The absorbance-concentration relationship is linear for samples containing up to 6 g/dl albumin. Bilirubin, moderate lipemia, and salicylate do not interfere with the analysis. The use of nonionic surfactant (Brij-35) reduces the absorbance of the blank, prevents turbidity and provides linearity. The results by this method agree very well with those obtained by electrophoresis and salt fractionation. The method is simple, it has excellent precision and the reagents are stable. A protein standard is introduced which can be employed for both the total serum proteins and albumin determinations.
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PMID:Albumin standards and the measurement of serum albumin with bromcresol green. 1971. 904 40

Taurine was used in the present study to evaluate its beneficial effects against proteinuria and hyperlipidemia associated with nephrotic syndrome. Rats made nephrotic with adriamycin had a high excretion of protein, albumin, and N-acetyl-beta-D-glucosaminidase compared with nonnephrotic rats. Nephrotic rats manifested hyperlipidemia with significant elevation in all major lipoprotein fractions. Treatment with taurine significantly suppressed adriamycin-induced proteinuria, albuminuria, and urinary excretion of N-acetyl-beta-D-glucosaminidase. Treatment of rats wit taurine for 7 days before adriamycin, and daily thereafter, significantly lowered plasma cholesterol, triglycerides, phospholipids, lipid peroxides, and malondialdehyde associated with lipoprotein fractions. Similarly, total lipids, cholesterol, triglycerides, lipid peroxides, hydroperoxides, and hydroxyl radicals in the liver and kidneys of taurine-treated adriamycin rats were decreased significantly compared with adriamycin alone. Lecithin cholesterol acyl transferase activity and free fatty acid levels in plasma, lipoprotein lipase activity, glutathione, total thiol, and ascorbic acid in the liver and the kidneys of taurine-treated adriamycin groups were significantly elevated compared with adriamycin alone. These results suggest that taurine might be applicable as a protective agent for proteinuria and hyperlipidemia associated with nephrotic syndrome.
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PMID:Protection by taurine against adriamycin-induced proteinuria and hyperlipidemia in rats. 918 3

Though calcium plays an important role in a number of biologic processes related to the pathogenesis of atherosclerosis, the relationship of serum calcium and phosphorus levels with the angiographic severity of coronary artery disease (CAD) is not known. We retrospectively studied 376 stable patients (age range 31-86 years, mean 59.2 +/- 10.5 years; 68% males) undergoing routine coronary angiography and related the angiographic severity of CAD with the serum levels of total and corrected calcium, phosphorus, albumin, total protein and bicarbonate. The primary variable studied was the number of vessels with haemodynamically significant disease. On univariate analysis, total serum calcium and serum albumin levels had a negative association with the number of vessels diseased (P = 0.046 and 0.057, respectively). Multiple regression analysis using age, sex, smoking, diabetes, hypertension, hyperlipidaemia, ethnicity and family history, in addition to serum calcium, phosphorus and albumin levels as the predictor variables, showed that serum albumin has an independent negative and serum phosphorus has an independent positive association with the angiographic severity of CAD (P = 0.04 and 0.003, respectively; n = 294). Serum phosphorus level also showed highly significant positive associations with the presence of total or subtotal occlusion and with most severe stenosis observed on angiography. A moderate change in the serum level of albumin or phosphorus confers a risk similar to that associated with smoking, as estimated by the odds ratios.
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PMID:Serum calcium, phosphorus and albumin levels in relation to the angiographic severity of coronary artery disease. 920 42

Albumin deficiency is accompanied by a reduction in red cell deformability and blood hyperviscosity. Albumin deficiency increases plasma fibrinogen and triglyceride levels and may alter red cell membrane lipid composition. These options, which could all contribute to reduced red cell deformability (RCD) and hyperviscosity, were studied in the Nagase analbuminemic rat (NAR), a mutant Sprague Dawley rat (CON), characterized by normal total protein levels, with an absolute deficiency of albumin, but elevated levels of non-albumin proteins and hyperlipidemia. Plasma protein-binding of the polar phopholipid lysophosphatidylcholine (LPC) was markedly decreased. LPC comprised only 26 +/- 1% of total plasma phospholipids as compared to 42 +/- 2% in CON. NAR red cells in CON plasma had a viscosity that was similar to CON red cells in CON plasma. Conversely, CON red cells in NAR plasma show an increased viscosity as compared to CON red cells in CON plasma. The maximum deformation index of both NAR and CON red cells was markedly decreased in NAR plasma as compared to either NAR or CON cells in CON plasma (0.04 +/- 0.03 and 0.02 +/- 0.02 vs. 0.22 +/- 0.06 and 0.15 +/- 0.04, respectively; P < 0.05). Thus, plasma composition causes hyperviscosity and reduced RCD in NAR. Fibrinogen is not responsible since red cells in serum and red cells in plasma had a similar viscosity and differences in viscosity and RCD between NAR and CON were maintained. Plasma triglycerides are also not responsible since the viscosity of red cells in serum with a 50% reduction in triglycerides was not reduced. LPC levels in red cells were increased in NAR (8.7 +/- 0.2 vs. 5.5 +/- 0.3% of total phospholipids; P < 0.01). Adding albumin to NAR blood dose-dependently decreased whole blood viscosity, despite marked increases in plasma viscosity, and increased RCD of NAR cells (from 0.04 +/- 0.03 to 0.21 +/- 0.01; P < 0.05). There was also some effect on CON RCD of similar albumin addition to CON blood (from 0.15 +/- 0.04 to 0.29 +/- 0.03; P < 0.05). Adding albumin to NAR blood reduced red cell LPC content and increased plasma LPC content in a dose-dependent fashion, whereas there were only slight effects of adding albumin to CON blood. There was a reciprocal relation between red cell LPC and the other polar phospholipids in the red cell membrane, probably indicating exchange. The maximum deformability index of either NAR or CON cells was not affected much by adding LPC to CON plasma (NAR, from 0.22 +/- 0.06 to 0.18 +/- 0.10; CON, from 0.15 +/- 0.04 to 0.12 +/- 0.05; NS), whereas adding LPC to NAR plasma caused the red cells to become rigid. Adding LPC to CON red cells in NAR plasma caused a much stronger increase in relative LPC content (from 6.6 +/- 0.7 to 10.9 +/- 0.9%; P < 0.05) than adding LPC to CON red cells in CON plasma (from 5.6 +/- 0.4 to 6.4 +/- 0.8%; NS). Thus, in the absence of albumin, LPC in red blood cells is increased. As a consequence of the latter, RCD is decreased and whole blood viscosity increased. Alterations in red cell phospholipids are far more important than increases in plasma fibrinogen or triglycerides in determining hyperviscosity of blood and reduced RCD in NAR.
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PMID:Hypoalbuminemia causes high blood viscosity by increasing red cell lysophosphatidylcholine. 929 Nov 98

Polymerized hemoglobin solutions (Hb-based oxygen carriers; HBOCs) and a second-generation perfluorocarbon (PFC) emulsion (Perflubron) are in clinical trials as temporary oxygen carriers ("blood substitutes"). Plasma and serum samples from patients receiving HBOCs look markedly red, whereas those from patients receiving PFC appear to be lipemic. Because hemolysis and lipemia are well-known interferents in many assays, we examined the effects of these substances on clinical chemistry, immunoassay, therapeutic drug, and coagulation tests. HBOC concentrations up to 50 g/L caused essentially no interference for Na, K, Cl, urea, total CO2, P, uric acid, Mg, creatinine, and glucose values determined by the Hitachi 747 or Vitros 750 analyzers (or both) or for immunoassays of lidocaine, N-acetylprocainamide, procainamide, digoxin, phenytoin, quinidine, or theophylline performed on the Abbott AxSym or TDx. Gentamycin and vancomycin assays on the AxSym exhibited a significant positive and negative interference, respectively. Immunoassays for TSH on the Abbott IMx and for troponin I on the Dade Stratus were unaffected by HBOC at this concentration. Tests for total protein, albumin, LDH, AST, ALT, GGT, amylase, lipase, and cholesterol were significantly affected to various extents at different HBOC concentrations on the Hitachi 747 and Vitros 750. The CK-MB assay on the Stratus exhibited a negative interference at 5 g/L HBOC. HBOC interference in coagulation tests was method-dependent-fibrometer-based methods on the BBL Fibro System were free from interference, but optical-based methods on the MLA 1000C exhibited interferences at 20 g/L HBOC. A 1:20 dilution of the PFC-based oxygen carrier (600 g/L) caused no interference on any of these chemistry or immunoassay tests except for amylase and ammonia on the Vitros 750 and plasma iron on the Hitachi 747.
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PMID:Effect of hemoglobin- and Perflubron-based oxygen carriers on common clinical laboratory tests. 929 68

In the normal population, the usual effect of the epsilon 2 allele is to decrease plasma cholesterol and to increase plasma triglyceride. We report here the association of nephrotic syndrome and the apo epsilon 2 epsilon 2 genotype in which we observed a hyperlipidemia characterized by very low levels of lipoprotein lipase activity, chylomicronemia, high levels of plasma apo B, C III, E and lipoprotein(a), very low levels of high density lipoprotein cholesterol and concentrations of cholesterol and triglyceride that are higher than expected in all the other lipoprotein fractions. When proteinuria was partially resolved and plasma albumin levels returned to normal, a residual type III hyperlipidemia was still present. These findings suggest that the combination of apo epsilon 2 homozygosity and massive proteinuria may cause considerable changes in the clearance of triglyceride rich particles probably mediated by the almost complete absence of lipolytic enzymes and a low interaction of lipoproteins with specific receptors. The apo E genotype should be investigated in nephrotic patients with chylomicronemia.
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PMID:The influence of apoprotein epsilon 2 homozygosity on nephrotic hyperlipidemia. 934 84

In a study of structure-activity relationship with drug-induced nephropathy two lipoxygenase inhibitors, the N-hydroxyurea derivative 70C ((E)-N-{3-[3-(4-fluorophenoxy) phenyl]-1-(R, S)-methylprop-2-enyl}-N-hydroxyurea) and the N-hydroxamic acid analogue 360C ((E)-N-{3-[3-(4-fluorophenoxy) phenyl]-1-(R, S)-methylprop-2-enyl}-N-hydroxamic acid), were administered to rats. 70C and 360C were dosed to female Wistar rats at 100 mg/kg po daily for 7 days. Another group of rats was given a single intravenous bolus dose of puromycin aminonucleoside (PAN) at 100 mg/kg. Urine samples were collected from all groups during the study and plasma samples were collected after 7 days. Kidneys were excised and fixed for examination by electron microscopy. 70C- and PAN-treated groups both showed early changes in the glomeruli, in which the visceral cells appeared enlarged and showed varying degrees of foot process loss. This foot process loss was associated with decreases in total plasma protein and albumin and increases in the plasma cholesterol, triglycerides, creatinine, and urea were recorded. Marked proteinuria was observed in both the 70C and PAN groups. The foot process loss together with increased proteinuria, hypoalbuminemia, hypercholesterolemia, and lipemia are all characteristic of the human condition, Minimal Change Nephrotic Syndrome. All the biochemical and morphological investigations showed that 360C-treated rats were similar to the control group, suggesting that the hydroxyurea moiety of 70C is responsible, either directly or indirectly, for the induction of the nephrotic syndrome seen in rats.
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PMID:Structure-activity relationship for two lipoxygenase inhibitors and their potential for inducing nephrotic syndrome. 934 98

Life expectancy is shorter in the subset of insulin-dependent diabetic (IDDM) patients who are susceptible to kidney disease. Familial factors may be important. In this study the prevalence of cardiovascular disease mortality and morbidity and of risk factors for cardiovascular disease was compared in the parents of 31 IDDM patients with elevated albumin excretion rate (AER > 45 microg/min; group A) with that of parents of 31 insulin-dependent diabetic patients with normoalbuminuria (AER < 20 microg/min; group B). The two diabetic patient groups were matched for age and duration of disease. Information on deceased parents was obtained from death certificates and clinical records and morbidity for cardiovascular disease was ascertained using the World Health Organization questionnaire and Minnesota coded ECG. Hyperlipidaemia was defined as serum cholesterol higher than 6 mmol/l and/or plasma triglycerides higher than 2.3 mmol/l and/or lipid lowering therapy; arterial hypertension as systolic blood pressure higher than 140 mmHg and/or diastolic blood pressure higher than 90 mmHg and/or antihypertensive treatment. The percentage of dead parents was similar in the two groups (26 vs 20% for parents of group A vs group B, respectively), but the parents of the diabetic patients with elevated AER had died at a younger age (58 +/- 10 vs 70 +/- 14 years; p < 0.05). Parents of diabetic patients with nephropathy had a more than three times greater frequency of combined mortality and morbidity for cardiovascular disease than that of the parents of diabetic patients without nephropathy (26 vs 8%; odds ratio 3.96, 95% CI 1.3 to 12.2; p < 0.02). Living parents of group A had a higher prevalence of arterial hypertension (42 vs 14% p < 0.01) and hyperlipidaemia (49 vs 26% p < 0.05) as well as higher levels of lipoprotein (a) [median (range) 27.2 (1-107) vs 15.6 (0.2-98) mg/dl; p < 0.05]. They also had reduced insulin sensitivity [insulin tolerance test: median (range) K(itt) index: 3.7 (0.7-6.2) vs 4.8 (0.7-6.7)% per min; p < 0.05]. In the families of IDDM patients with elevated AER there was a higher frequency of risk factors for cardiovascular disease as well as a predisposition to cardiovascular disease events. This may help explain, in part, the high prevalence of cardiovascular disease mortality and morbidity in those IDDM patients who develop nephropathy.
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PMID:High prevalence of risk factors for cardiovascular disease in parents of IDDM patients with albuminuria. 934 1


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