UMLS:C0020473 - FACTA Search

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

The metabolic origins of equine hyperlipaemia were investigated by analysing the concentration and composition of plasma lipoproteins in 18 ponies with the condition. The mean concentrations of cholesterol, triglyceride and very low density lipoproteins (VLDL) were increased by 4-, 52- and 19-fold, respectively, compared with a control group of 18 healthy ponies. These increases were due to the appearance of a buoyant VLDL fraction (VLDL1) not present in healthy ponies. The mean diameter of VLDL1 particles was 44% greater than control VLDL, and the particles were enriched in triglyceride and free cholesterol and depleted of cholesteryl esters, phospholipid and protein. The apolipoprotein (apo) B-100 content of VLDL1 was reduced and the ratio of apoB-100 to apoB-48 particles was 1:1, compared with 2:1 in control VLDL. The VLDL1 was also enriched in apoE, but had normal complements of apoC-II and apoC-III. The conventional VLDL (called VLDL2), LDL and HDL fractions were moderately enriched with triglyceride, and HDL contained increased amounts of apoE, apoC-II and apoC-III. The activities of lipoprotein lipase and hepatic lipase, the enzymes responsible for the catabolism of VLDL and their remnants, were increased by 2- and 3-fold, respectively, in response to the increased concentrations of their substrates. The composition of VLDL1 suggested that the liver was maximising the secretion of triglyceride by producing larger number of VLDL particles that accommodated a greater mass of triglyceride by having apoB-48 rather than apoB-100 as their structural protein. Plasma free fatty acid (FFA) concentrations were elevated in 17 of the 18 ponies, suggesting that increased FFA flux might be the stimulus for hepatic triglyceride synthesis and VLDL secretion. We conclude that overproduction, rather than defective catabolism, of VLDL was the cause of the hyperlipidaemia and that lipid lowering agents which reduce VLDL synthesis, by decreasing adipose lipolysis and FFA flux, are candidates for the management of hyperlipaemia.
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PMID:Plasma lipids, lipoproteins and post-heparin lipases in ponies with hyperlipaemia. 139 7

Human high density lipoproteins2 (HDL2) consist of particles that contain both apolipoprotein (apo) A-I and apoA-II (A-I/A-II-HDL2) and others that contain apoA-I but are devoid of apoA-II (A-I-HDL2). When postprandial lipemia is pronounced, a fraction of HDL2 is converted into HDL2-like particles. These HDL3 exhibit lower apoA-I/apoA-II ratios than the parent HDL2, suggesting preferential conversion of A-I/A-II-HDL2 into HDL3 (J. Clin. Invest. 1984. 74: 2017-2023). Triglyceride transfer from triglyceride-rich lipoproteins to HDL2 and subsequent lipolysis by hepatic lipase are thought to mediate the conversion of HDL2 into HDL3. To understand why A-I/A-II-HDL2 are preferentially converted into HDL3, we separated postprandial HDL2 into A-I-HDL2 and A-I/A-II-HDL2 species by immunoaffinity chromatography using a monoclonal antibody for apoA-II, and determined the ability of HDL2 species i) to participate in protein-mediated lipid transfer; and ii) to interact with hepatic lipase in vitro. Triglyceride transfer from/to triglyceride-rich lipoproteins was similar for the two HDL2 species. In contrast, A-I/A-II-HDL2 were twice as effective as A-I-HDL2 in liberating hepatic lipase immobilized on HDL3-Sepharose. Lipolysis of triglycerides by hepatic lipase was 60% higher in postprandial A-I/A-II-HDL2 than in postprandial A-I-HDL2. Hydrolysis of phosphatidylcholine by hepatic lipase was threefold higher in A-II-containing HDL2 when compared with HDL2 devoid of apoA-II. The different lipolytic rates in HDL2 subspecies correlated with the size reduction of substrate lipoproteins. Reconstitution of postprandial A-I-HDL2 with apoA-II enhanced the rate of lipolysis by hepatic lipase to that observed in A-I/A-II-HDL2. We conclude that it is the interaction with hepatic lipase rather than the rate of triglyceride transfer that results in the preferred conversion of postprandial A-II-containing HDL2 into HDL3, and that apoA-II exerts a crucial role in this process.
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PMID:Different reactivities of high density lipoprotein2 subfractions with hepatic lipase. 140 96

Recent reports demonstrate a hypocholesterolaemic effect of daily subcutaneous injections of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in different rat models of hyperlipidaemia. However, this effect is not seen after oral administration of HMG-CoA reductase inhibitors in rats. We found that oral administration of the HMG-CoA reductase inhibitor Simvastatin also had no effect on plasma cholesterol in severely hyperlipidaemic Nagase analbuminaemic rats (NAR). Simvastatin (an apolar compound dissolved in propylene glycol) was infused continuously for 28 days into the subcutis of control Sprague-Dawley rats (SDR) and NAR using an implanted osmotic pump. All doses which were effective in reducing cholesterol in the NAR (reductions up to approximately 60%), reduced apolipoprotein AI but not apolipoprotein B and caused a severe inflammatory reaction in the dermis. Similar toxicity was observed in the SDR. Subcutaneous administration of the vehicle (propylene glycol) did not cause this reaction and did not affect plasma lipids. Administration of Lovastatin in osmotic pumps resulted in a similar inflammatory reaction. Incorporation of Simvastatin into liposomes did not diminish the toxic effect. On the other hand, infusion of Pravastatin (a polar HMG-CoA reductase inhibitor dissolved in isotonic saline) caused no changes in the dermis and had no effect on plasma lipids in NAR or SDR. Liver microsomes prepared from the Pravastatin-treated rats demonstrated a 3- to 4-fold increase in HMG-CoA reductase activity as compared to untreated rats, confirming uptake of the drug. We conclude that continuous subcutaneous administration of the HMG-CoA reductase inhibitors Simvastatin, Lovastatin and Pravastatin for 28 days may not reduce plasma cholesterol in rats by a mechanism which is related to inhibition of HMG-CoA reductase activity in the liver. The decrease of plasma cholesterol effected by subcutaneous infusion of Simvastatin or Lovastatin in NAR coincides with, and may be related to inflammatory changes caused by administering these compounds into the dermis.
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PMID:Subcutaneous administration of HMG-CoA reductase inhibitors in hyperlipidaemic and normal rats. 144 5

Uremic hyperlipidemia was recently suggested to contribute to progression of chronic renal failure (CRF). To investigate the relationship between lipoprotein abnormalities and decline of renal function, plasma lipids with apoproteins A1, B, E, CII, CIII, CII/CIII and E/CIII ratios, parathyroid hormone (PTH), insulin and glucose levels were examined in 72 patients with different degrees of CRF and compared to 28 patients of a reference group. A significant decrease of CII/CIII ratio was already evident below a Ccr of 60 ml/min, while increased apo-CIII and triglycerides (TG) with reduced HDL-cholesterol (HDL-C) levels occurred below a Ccr of 30 ml/min. Both TG and apo-CIII showed a positive correlation with creatinine levels. On the contrary, apo-CII/apo-CIII and HDL-C inversely correlated with the progression of renal failure. PTH and insulin showed a positive correlation with TG, the former being also inversely related to apo-CII/apo-CIII ratio. Our results point to early apolipoprotein changes in the course of CRF. Elevated apo-CIII and reduced apo-CII/apo-CIII ratio may be considered the most typical features of uremic hyperlipidemia and likely account for the impaired TG removal and the hypertriglyceridemia (HTG). Secondary hyperparathyroidism may contribute to reduce peripheral lipolytic activity and cause HTG. A contributory role of hyperlipidemia in the progression of renal disease is also supported.
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PMID:Lipids and apolipoproteins change during the progression of chronic renal failure. 145 39

Hyperlipidemia is a prominent feature of the nephrotic syndrome. Lipoprotein abnormalities include increased very low and low density lipoprotein (VLDL and LDL) cholesterol and variable reductions in high density lipoprotein (HDL) cholesterol. We hypothesized that plasma cholesteryl ester transfer protein (CETP), which influences the distribution of cholesteryl esters among the lipoproteins, might contribute to lipoprotein abnormalities in nephrotic syndrome. Plasma CETP, apolipoprotein and lipoprotein concentrations were measured in 14 consecutive untreated and 7 treated nephrotic patients, 5 patients with primary hypertriglyceridemia, and 18 normolipidemic controls. Patients with nephrotic syndrome displayed increased plasma concentrations of apoB, VLDL, and LDL cholesterol. The VLDL was enriched with cholesteryl ester (CE), shown by a CE/triglyceride (TG) ratio approximately twice that in normolipidemic or hypertriglyceridemic controls (P < 0.001). Plasma CETP concentration was increased in patients with untreated nephrotic syndrome compared to controls (3.6 vs. 2.3 mg/l, P < 0.001), and was positively correlated with the CE concentration in VLDL (r = 0.69, P = 0.004) and with plasma apoB concentration (r = 0.68, P = 0.007). Treatment with corticosteroids resulted in normalization of plasma CETP and of the CE/TG ratio in VLDL. An inverse correlation between plasma CETP and HDL cholesterol was observed in hypertriglyceridemic nephrotic syndrome patients (r = -0.67, P = 0.03). The dyslipidemia of nephrotic syndrome includes increased levels of apoB-lipoproteins and VLDL that are unusually enriched in CE and likely to be atherogenic. Increased plasma CETP probably plays a significant role in the enrichment of VLDL with CE, and may also contribute to increased concentrations of apoB-lipoproteins and decreased HDL cholesterol in some patients.
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PMID:Increased concentration of plasma cholesteryl ester transfer protein in nephrotic syndrome: role in dyslipidemia. 147 91

Familial combined hyperlipidemia (FCHL) appears to be the most common, simply inherited hyperlipidemia strongly associated with coronary heart disease. In the family examined in this study, two of the siblings who met diagnostic criteria for FCHL had extensive clinical atherosclerosis before age 30, unusually premature for this form of hyperlipidemia. Lipoproteins and low-density lipoprotein (LDL) apolipoprotein (apo) B metabolism were characterized in these siblings in an attempt to gain insight into the cause of the rapid atherosclerosis in the two siblings so affected. LDL apo B production rates were very high in all three siblings (25 to 30 mg/kg/d), consistent with FCHL. beta-Very-low-density lipoprotein-beta (beta-VLDL) was present in the plasma of both siblings with accelerated atherosclerosis. The isoapolipoprotein E pattern in both of these siblings was E-3/E-2. In the third sibling, who was free of premature clinical atherosclerosis and lacked plasma beta-VLDL, the pattern was E-3/E-3. Thus, the heterozygote apo E-3/E-2 pattern may be related to the accumulation of beta-VLDL in persons with a very high apo B production rate. The abnormal accumulation of beta-VLDL may be one of the possible explanations for the rapid, premature atherosclerosis in the two siblings with FCHL in this kindred. Both male members in this kindred also had low levels of high-density lipoproteins, and thus may have had an additional risk of developing atherosclerosis due to this lipoprotein abnormality as well.
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PMID:Metabolism of apolipoprotein B in members of a family with accelerated atherosclerosis: influence of apolipoprotein E-3/E-2 pattern. 154 61

Twenty-five patients with a renal transplant for 15 months to 19.4 years, hyperlipidaemia and stable graft function underwent three months of dietary management. Plasma lipid and apolipoprotein concentrations and lipoprotein electrophoresis were measured after a 12 hour fast at enrollment and after three months of diet. The aims of diet were to reduce energy intake in the overweight, restrict fat to 25-30% of total intake, reduce saturated fat content to less than 10% of total energy and cholesterol to less than 300 mg/d. After three months of diet there was a significant fall in mean cholesterol/HDL cholesterol risk ratio and a rise in mean HDL cholesterol concentration. Six patients reverted to a normal lipoprotein electrophoretic pattern with a significant reduction in mean total cholesterol, LDL cholesterol, cholesterol/HDL cholesterol ratio, apoprotein B and apoB/apo A-1 ratio. Most of the other patients who made dietary modifications showed some improvement in their lipid parameters. Dietary modification should be the initial approach to the management of posttransplant hyperlipidaemia.
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PMID:Effect of diet on posttransplant hyperlipidaemia. 154 40

To investigate possible genetic influences on plasma apolipoprotein (apo) B levels in familial combined hyperlipidemia (FCHL), commingling analysis was performed on data from seven large kindreds, including 183 individuals. The overall frequency distribution of apo B was skewed and was compatible with the presence of two normally distributed subdistributions (mean values, 117 and 172 mg/dl). The analysis was repeated after stratification of individuals by low density lipoprotein (LDL) subclass phenotype. Among subjects with phenotype A (predominance of large, buoyant LDL), a single apo B distribution was found (mean, 115 mg/dl). Among subjects with phenotype B (predominance of small, dense LDL), the distribution was bimodal, with mean values, 116 and 167 mg/dl, similar to the unstratified data set. Thus the skewing of the overall apo B distribution in FCHL family members may be due to a distinct subset of individuals with phenotype B who are genetically susceptible to even higher elevations of apo B. The higher apo B/phenotype B subjects also showed significantly higher levels of triglyceride and LDL-cholesterol than the lower apo B/phenotype B subjects. The lower apo B/phenotype B subjects had higher triglyceride and lower LDL-cholesterol than the phenotype A subjects. The enhanced information regarding apo B and lipid levels in the three subgroups of individuals identified here may facilitate a better understanding of genetic susceptibility to coronary heart disease.
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PMID:Bimodality of plasma apolipoprotein B levels in familial combined hyperlipidemia. 157 22

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

The nephrotic syndrome results from altered glomerular permselectivity, causing urinary protein loss, reduced albumin concentration, oncotic pressure (pi), and hyperlipidemia. Hepatic lipid and apolipoprotein synthesis increases and lipoprotein catabolism decreases. Decreased lipoprotein catabolism follows the onset of proteinuria but is not associated with hereditary analbuminemia [Nagase analbuminemic rat (NAR)] if proteinuria is absent. We measured plasma apolipoproteins (apo) AI, B, and E levels, their mRNA concentrations in liver, and the transcription rate of each mRNA in rats with Heymann nephritis (HN) or NAR to determine which alterations occurred in NAR alone without proteinuria. Plasma apo AI, B, and E were increased in both HN and NAR. Cholesterol and apo AI were inversely proportional to pi and independent of urinary protein loss or the presence of albumin in plasma. In contrast, triglycerides (TGs) were significantly greater in HN and were increased out of proportion to apo B. The concentration of apo AI mRNA increased in liver of both HN and NAR as did apo AI transcription. Apo E mRNA increased in neither HN nor NAR, whereas apo B mRNA increased only in HN. Transcription of neither apo B nor E increased. Plasma apo AI levels are likely to be regulated transcriptionally at the level of protein synthesis, whereas plasma apo B and E levels are regulated either posttranscriptionally, at the level of protein catabolism, or at both sites. Lipoproteins rich in TG and poor in apo B appear after the development of proteinuria but not as a consequence of analbuminemia alone. The accumulation of TG-rich apo B containing lipoproteins in rats with HN may result from impaired lipolysis occurring as a consequence of proteinuria.
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PMID:Apolipoprotein gene expression in analbuminemic rats and in rats with Heymann nephritis. 159 Apr 20

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