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)

Serum concentrations of apolipoprotein(a) [apo(a)], the unique glycoprotein of lipoprotein(a), are increased in patients with end-stage renal failure. We prospectively studied serum apo(a) and other lipoproteins in 20 consecutive patients, ages 46 +/- 11 years, before and for six months after successful renal transplantation. All patients received cyclosporine, and no patient was treated for hyperlipidemia. The mean creatinine clearance increased from 7.5 mL/min before transplant surgery to 40.9 mL/min six months afterwards (P less than 0.001). Apo(a) decreased from a median of 403 units/L before transplantation to 184 units/L at one week (P less than 0.001) and was 170 units/L (P less than 0.001) at six months. For the assay used, 1 unit of apo(a) is equivalent to 1 mg of lipoprotein(a). In contrast, from baseline to six months, increases were found for low-density lipoprotein (LDL) cholesterol (P = 0.03), high-density lipoprotein cholesterol (P = 0.06), apo B (P = 0.07), and apo A-I (P = 0.01). The decrease in apo(a) in individual patients was significantly correlated with the increase in creatinine clearance (r = -0.48, P less than 0.001). The single patient who developed nephrotic syndrome after renal transplantation had marked increases in apo(a) (693-1595 units/L), apo B, and LDL cholesterol, which paralleled the degree of proteinuria. These findings suggest that abnormal renal function affects the regulation of lipoprotein(a) metabolism.
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PMID:Decreases in apolipoprotein(a) after renal transplantation: implications for lipoprotein(a) metabolism. 154 51

Hypercholesterolemia is commonly associated with primary biliary cirrhosis. In the general population, elevated serum cholesterol is associated with an increased risk of atherosclerosis. The relative risk has been poorly defined in primary biliary cirrhosis patients with hyperlipidemia. In addition, the hyperlipidemic state seen with primary biliary cirrhosis has not been well studied. We prospectively observed 312 patients with primary biliary cirrhosis for a median of 7.4 yr. During this period, 128 patients died. The incidence of atherosclerotic death in patients with primary biliary cirrhosis was not statistically different when compared with an age-matched and sex-matched U.S. control population. A similar group of 50 consecutive PBC patients had detailed serum lipid profiles. Findings included progressive increases in total cholesterol and low-density lipoprotein cholesterol with an increasing histological stage or severity of disease. High-density lipoprotein cholesterol was elevated in all stages, with the highest levels in histological stage 2 and 3 disease. Triglycerides were normal or slightly elevated in all stages. Apoprotein A-I was elevated in all but histological stage 4 disease. Our study suggests the hyperlipidemia associated with primary biliary cirrhosis does not place these patients at risk for atherosclerotic death. In light of the limitations imposed by our relatively small sample size, however, additional patients should be studied. Furthermore, an examination of the pathophysiological mechanisms leading to hypercholesterolemia should be the topic of further study.
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PMID:Hypercholesterolemia and atherosclerosis in primary biliary cirrhosis: what is the risk? 156 27

The present study evaluated indomethacin therapy--a nonsteroidal anti-inflammatory drug--on experimental hyperlipidemia and atherosclerosis in Rhesus monkeys. Twenty-four monkeys were divided randomly into four groups of six. Two groups received stock pellet diet and two were given an atherogenic diet for six months. After this period, one stock diet-fed group and one atherogenic diet-fed group were treated with oral indomethacin (2.5 mg) on alternate days for a further six months. Serum lipids and lipoproteins were markedly elevated in atherogenic diet-fed monkeys. Generally, indomethacin did not exert a hypocholesterolemic effect; however, liver cholesterol was decreased (P less than 0.05) in atherogenic diet-fed monkeys treated with indomethacin. High density lipoprotein cholesterol was increased in stock diet-fed, indomethacin-treated monkeys but not in atherogenic diet-fed, indomethacin-treated monkeys. Apoprotein A-I was not affected by indomethacin in either stock or atherogenic diet-fed monkeys; however, the drug produced a significant (P less than 0.01) reduction of serum thromboxane B2 in stock diet-fed monkeys, without restoring the 6-keto-prostaglandin F1 alpha to pretreatment levels. A protective role of the drug was noted on both the extent and severity of aortic and coronary atherosclerosis.
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PMID:Effect of indomethacin on serum lipids, lipoproteins, prostaglandins and the extent and severity of atherosclerosis in rhesus monkeys. 157 66

Two sandwich-type enzyme immunoassays have been developed to measure apolipoproteins A-I and E in rabbit serum. Specific goat antibodies were purified by affinity chromatography and used both for coating and for preparing antibody-peroxydase conjugates. The sensitivity of these assays is sufficient to allow studies of apo A-I and E distribution in lipoproteins fractionated by gel filtration from 50 microliters of serum. In WHHL rabbits, apo A-I is 5-fold lower (5.2 +/- 2.5 mg/dl) and apo E is 8-fold higher (9.9 +/- 3.5 mg/dl) than in normolipidemic rabbits (29 +/- 4.3 mg/dl and 1.3 +/- 0.5 mg/dl, respectively). In hyperlipidemic rabbits, fed 2 months on a 0.5% cholesterol diet, the apo A-I level was similar (32 +/- 12 mg/dl) to that of normolipidemic rabbits, but the apo E level is 12-fold higher (15.1 +/- 5.5 mg/dl). In addition, HDL particles were enriched with cholesterol and apo E. The bulk of apo E and cholesterol is located in large beta-VLDL in diet-induced hyperlipidemia, whereas they are mainly located in smaller size beta-VLDL in WHHL rabbits. In normolipidemic rabbits apo E occurs mainly in HDL, and cholesterol is distributed in the main three lipoprotein fractions VLDL, LDL and HDL. Interestingly, HDL of WHHL rabbit are deficient in apo A-I. These results are compatible with profound perturbations of lipoprotein composition and metabolism in atherogenic hyperlipidemia.
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PMID:Concentration and distribution of apolipoproteins A-I and E in normolipidemic, WHHL and diet-induced hyperlipidemic rabbit sera. 164 96

The abnormalities of lipid metabolism in nephrotic syndrome consist in an increase in total and low-density lipoprotein (LDL) cholesterol, apolipoproteins B (ApoB), C-II and C-III, associated in patients with heavier or marked hypoalbuminemia with an increase in triglycerides and very low-density lipoprotein (VLDL) cholesterol, while the high-density lipoproteins (HDL) are distributed abnormally (increased HDL3 fraction and decreased HDL2 fraction) and the Apo A-I to Apo B ratio is reduced. Both increased hepatic lipoprotein synthesis and reduced removal capacity contribute to this hyperlipidemia. Proteinuria may lead to the lipoprotein abnormalities through stimulation of VLDL synthesis by the liver induced by hypoalbuminemia, although it has been more recently suggested that urinary protein loss is associated with the urinary loss of some important cofactor for the regulation of lipid synthesis or catabolism. Treatment of lipid abnormalities in patients with long-lasting heavy proteinuria is mandatory, because they may cause or contribute to accelerated atherosclerosis, but also because they appear to accelerate progression of renal disease by favouring mesangial sclerosis. Four groups of lipid-lowering drugs have been tested: 1) bile acid-binding resins; 2) fibric acid; 3) probucol; 4) inhibitors of HMG CoA reductase. The drugs of the last group appear to be effective and safe in short-term experiments, but long-term studies are necessary to confirm their validity. A dietary approach, consisting in a strictly vegetarian soy diet, very rich in poly- and monounsaturates fatty acids, has been recently tested by the author, with very promising results.
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PMID:Lipid changes in the nephrotic syndrome: new insights into pathomechanisms and treatment. 175 84

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.
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PMID:Hyperlipoproteinemia in Nagase analbuminemic rats: effects of pravastatin on plasma (apo)lipoproteins and lecithin:cholesterol acyltransferase activity. 177 Feb 92

HMG-CoA reductase inhibitors have been proven effective in decreasing the plasma cholesterol levels in patients affected with various forms of hypercholesterolemia, familial dysbetalipoproteinemia, familial combined hyperlipidemia and in nephrotic and diabetic dyslipidemia. The purpose of this study was to monitor and evaluate the efficiency and safety of the therapy with simvastatin, an HMG-CoA reductase inhibitor, in a group of patients treated by continuous ambulatory peritoneal dialysis (CAPD) with severe hypercholesterolemia. Monitoring of the changes occurring in the various lipids and apolipoproteins in these patients included the measurements of the plasma lipids and apolipoproteins A-I, A-II, B, C-II, A-IV and Lp(a). Lipoproteins were separated by gel filtration, on a Superose 6HR column, before and after 24 weeks of treatment. The patterns were compared to those observed in a group of primary hyperlipidemic patients treated with Lovastatin, a compound of the same class. The drug was well tolerated by the CAPD patients and no adverse reaction was observed. In addition to the decrease of the total and LDL cholesterol, similar to that reported in other groups of patients, we further observed a decrease of the apo E concentration in both the CAPD and the hyperlipidemic patients. This decrease was especially pronounced in the HDLE fraction and could involve an upregulation of the apo B-E and/or apo E receptor. These results should provide information about the mechanism of action of this drug in patients with end-stage renal disease.
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PMID:Effect of simvastatin treatment on the dyslipoproteinemia in CAPD patients. 187 12

The purpose of the study was to try to detect at an early stage the important cardiovascular risk factors associated with increased concentrations of blood lipids, notably cholesterol. The trial was based on the screening of 102 families, including 219 children, 8-18 years of age and their parents. A group of young adults, 19-25 years of age, was included in the study. All subjects were derived from a paediatric practice. In addition to total cholesterol, VLDL-, LDL-, HDL-cholesterol and apolipoproteins A-I and B were also measured. The study identified a significant number of school-children and adolescents with hyperlipidaemia, predominantly hypercholesterolaemias type II-A. There was a close relationship between their blood lipids and those of their parents. The study demonstrates the importance of including parents in studies of this kind. Total cholesterol proved to be a reliable parameter for screening. The value of apolipoproteins in such screening is discussed.
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PMID:Lipid screening in paediatrics for early detection of cardiovascular risks. 210 83

Assessment of the relative transcription rates and mRNA steady-state levels for apolipoprotein genes E, A-I, and A-II has been performed in normal rat liver, during liver regeneration and following induction of cirrhosis, as well as in rats with inherited analbuminemia associated with hyperlipidemia. Apo E exhibits primarily transcriptional control with an additional component of posttranscriptional control, whereas Apo A-I is controlled primarily at the posttranscriptional level, thus indicating that these genes are regulated independently. The level of control for Apo A-II has not been determined, because of difficulty experienced in measuring the transcription rate of this gene. During liver regeneration, cirrhosis, and analbuminemia, there is a marked increase in the ratio of Apo A-I to Apo E mRNA, resulting from an increase in the Apo A-I mRNA steady-state level and a decrease in Apo E mRNA. These changes are similar in the three pathophysiologic states and seem to occur through a combination of transcriptional and posttranscriptional mechanisms.
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PMID:Transcriptional and posttranscriptional regulation of apolipoprotein E, A-I, and A-II gene expression in normal rat liver and during several pathophysiologic states. 212 16

The ability of glycosaminoglycans to bind to a wide number of biologically active macromolecules has already been investigated. Recent clinical trials on the possible therapeutic benefits of glycosaminoglycans must be placed in perspective, even if they appear to be particularly encouraging, especially as regards the glycosaminoglycan effects on certain coagulation factors. A multicenter, medium-term, double-blind, crossover trial was performed by several Italian Lipid Clinics to determine whether administration of a medium molecular weight glycosaminoglycan (Sulodexide) has a significant clinical effect. Patients affected by peripheral vascular disease and/or hyperlipidemia (type IIa, IIb and IV) were submitted to a 4-week wash-out period, followed by parenteral Sulodexide (S) or placebo (P) administration for 2 weeks, another 2 week wash-out period, parenteral crossover drug or P administration for 2 weeks and, finally, oral S administration for 6 months. Sulodexide lowered plasma viscosity and plasma fibrinogen in all patients. There was also a drop in triglycerides together with a rise in apo A-I and HDL-C in type IV hyperlipoproteinemics, whereas there was no significant effect on total or LDL-plasma cholesterol in type IIa and IIb patients. Moreover, there was a percent increase in peak flow and rest flow in the lower limbs of peripheral vascular disease patients. No side effects or intolerance phenomena were detected. The results indicate that Sulodexide administration may be useful in long-term treatment of patients with peripheral vascular disease and a concomitant increase in plasma triglycerides and/or fibrinogen and/or viscosity.
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PMID:Double-blind multicenter trial on a new medium molecular weight glycosaminoglycan. Current therapeutic effects and perspectives for clinical use. 219 May 65


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