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)

Detected using a method involving gradient electrophoresis on polyacrylamide gel, the presence of a high level of an Lp(a) was demonstrated in 17% of control subjects and 39% oh hyperlipidaemic subjects explored. The difference appeared to be particularly significant in subjects with a pure hypercholesterolaemia (type IIA) or dominant hypercholesterolaemia (type IIB), which may be accounted for by the antigenic communities and related substances in the lipid composition uniting Lp(a) to LDL. The association of frank atherosclerosis with the hyperlipidaemia substantially increased the frequency of high levels of circulating Lp(a). A combined elevation of levels of Lp(a) and LDL would seem to be associated with a particular atherogenic power.
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PMID:[Detection of a new lipoprotein: Lp(a). Its occurrence in atherosclerosis with or without hyperlipemia]. 7 59

Probucol, which decreases cholesterol levels and has antioxidant properties, was administered orally to patients with familial combined hyperlipidemia and high plasma lipoprotein(a) [Lp(a)] levels. The drug had no effect on Lp(a) concentrations after 4 weeks, but was found to be distributed in both Lp(a) and low-density lipoprotein (LDL). Before treatment, in each case LDL and Lp(a) isolated from the same individual were readily oxidized by copper, resulting in increased electrophoretic mobility and enhanced uptake and degradation by macrophages of both lipoproteins. After probucol treatment, both lipoproteins acquired resistance to in vitro oxidation by copper. Furthermore, probucol prevented their enhanced uptake and degradation by the macrophages. It is surmised that oxidized Lp(a) may carry an atherogenic potential that could be opposed by probucol administration.
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PMID:Probucol protects lipoprotein (a) against oxidative modification. 143 95

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

Hyperlipidemia poses a risk for cardiovascular disease in both hemodialysis and renal transplantation patients. Although lipid profiles differ between the 2 populations, we evaluated the possibility that both groups have similar abnormalities of lipoprotein(a) [Lp(a)]. Mean serum Lp(a) and standard error of the mean (SEM) in hemodialysis and transplant recipients was 16.6 +/- 4.7 and 18.3 +/- 3.6 mg/dl, respectively, compared with 10.7 +/- 4.1 mg/dl in healthy controls, p less than 0.05. That serum Lp(a) levels are significantly elevated in dialysis and renal transplantation patients suggests at least 1 common pathogenic mechanism for the high incidence of atherosclerosis in both groups.
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PMID:Elevated lipoprotein(a) levels in renal transplantation and hemodialysis patients. 184 Feb 33

Increased cholesterol levels above 200 mg/dl, LDL levels above 130 mg/dl and total cholesterol/HDL ratio above 4.5 in males and above 5.0 in females are recognized as indicators of increased risk of atherosclerosis. Risk associated to increased triglyceride levels (above 200 mg/dl) must be judged in relation to associated factors such as family history of coronary heart disease, presence of remnants (type III hyperlipidemia), presence of Lp(a), increased levels of Apo B, reduced levels of HDL2 or Apo A1. VLDL and chylomicron remnants and Lp(a) have an atherogenic power in vitro 2 to 4 times that of LDL. There is a correlation between hypertriglyceridemia and reduced HDL2 and Apo A1 levels. Hypertriglyceridemia is frequently associated to other risk factors like diabetes, obesity, hyperinsulinism, and high blood pressure. Finally, VLDL may elevate levels of plasma plasminogen inhibitor. Thus, hypertriglyceridemia should be investigated when, evaluating risk of atherosclerosis.
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PMID:[Cholesterol and triglycerides in atherosclerosis: epidemiologic and physiopathologic considerations]. 184

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

CAD results from atherosclerosis, a chronic disease process that has its origin in childhood. Children and adolescents can be at higher risk for CAD by virtue of being from families with premature CAD or familial dyslipoproteinemias. The plasma lipid and lipoprotein levels result from a number of complex metabolic processes that are under the control of genetic and environmental (e.g., diet) influences. The normal ranges of plasma lipids and lipoproteins in children are known, and children and adolescents with dyslipoproteinemia are ordinarily defined as those having levels of plasma total, LDL, or triglyceride above the 95th percentile or with a low HDL cholesterol below the 5th percentile. Children of a parent with documented dyslipoproteinemia or with family history of premature CAD may be screened in the fasting state any time after 2 years of age. Following the exclusion of secondary causes of dyslipoproteinemia, the diagnosis of primary dyslipoproteinemia can be made. Lipoprotein patterns are not diagnostic for a given genotype. Efforts to determine further the biochemical defects responsible for a given phenotype have led to the investigation of gene coding for the apolipoproteins, the key enzymes in the lipoproteins pathways (LPL, HDL, and LCAT) and the receptors that process lipoproteins, such as the LDL receptor and the chylomicron remnant receptor. From a practical standpoint, the diagnosis of the kind of dyslipoproteinemia in a child will depend upon the nature and severity of the dyslipoproteinemia, both in the child (or adolescent) and in parents and siblings. Marked increases in plasma total and LDL cholesterol in the child and in at least one of the parents often reflect the presence of familial hypercholesterolemia, an inherited dominant condition due to a defect in the LDL receptor gene. The triglyceride levels are often normal. If the child has a different dyslipoproteinemia pattern from siblings and parents, then the diagnosis of familial combined hyperlipidemia or hyperapobetalipoproteinemia should be considered. Most children with mild or borderline elevations in total and LDL cholesterol will have polygenic hypercholesterolemia. Triglyceride problems in children and adolescents are relatively uncommon, particularly the more severe hypertriglyceridemia such as that found in lipoprotein lipase and apoC-II deficiency, dysbetalipoproteinemia, and type V hyperlipoproteinemia. High levels of Lp(a) lipoprotein, in isolation or in combination with other dyslipoproteinemia, accelerate risk for CAD. Low levels of HDL cholesterol in the absence of other abnormalities suggest the diagnosis of hypoalphalipoproteinemia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Diagnosis and management of familial dyslipoproteinemia in children and adolescents. 225 50

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

Apoprotein, lipoprotein and lipid parameters of 36 normolipidemic subjects (23 males, mean age 22.7 +/- 7.6 years; 13 females, mean age 26.2 +/- 9.8 years) receiving oral isotretinoin (mean daily dose 0.73 +/- 0.26 mg/kg body weight) for nodulocystic acne (n = 18), severe acne papulopustulosa (n = 15), gram-negative folliculitis (n = 2) and papulopustular rosacea (n = 1) were monitored before and during isotretinoin therapy at biweekly intervals over a period of 14.6 +/- 5.6 weeks. Pretreatment values of mean plasma triglycerides increased significantly (p less than 0.001) from 81.8 +/- 31.9 mg/dl to 112.4 +/- 38.7 mg/dl (47.4%) during isotretinoin treatment. With respect to the mean percent increase of plasma triglycerides from pretreatment levels, patients were classified as nonresponders (less than 10% triglyceride increase), responders (greater than 10% less than 50% triglyceride increase) and hyperresponders (greater than 50% triglyceride increase), revealing a distribution of 25.0, 36.1 and 38.9%, respectively. Isotretinoin treatment had no influence on the isoelectric focusing pattern of apoprotein E isoforms and C apoproteins. In particular, apoprotein C-II, the cofactor of lipoprotein lipase, was not affected. No correlation between apoprotein E phenotypes (2/3, 3/3, 3/4) and the mean plasma triglyceride increase could be demonstrated. Apoprotein B-48, a marker of chylomicrons and atherogenic chylomicron remnants, could not be detected by SDS-PAGE. On the other hand in 21.0% of patients with preexisting mean lipoprotein Lp(a) levels of 18.1 +/- 12.9 mg/dl a moderate increase of atherogenic Lp(a) to mean levels of 37.0 +/- 22.0 mg/dl was observed. Pretreatment values of very-low-density lipoprotein (VLDL) apoprotein (apo) B (7.5 +/- 2.0 mg/dl), low-density lipoprotein apo B (67.3 +/- 17.5 mg/dl) and total plasma apo B (76.6 +/- 19.0 mg/dl) increased significantly to levels of 10.3 +/- 2.4 mg/dl (p less than 0.001), 75.7 +/- 15.8 mg/dl (p less than 0.10) and 85.9 +/- 17.7 mg/dl (p less than 0.05), respectively. As lipoprotein lipase and hepatic lipase activities have been shown to be unaffected by isotretinoin treatment, our data support the hypothesis that isotretinoin induces hepatic oversecretion of VLDL, a condition resembling type IV hyperlipidemia in diabetics, familial hypertriglyceridemia of familial combined hyperlipidemia.
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PMID:Characterization of apoprotein metabolism and atherogenic lipoproteins during oral isotretinoin treatment. 296 29

Genetic polymorphism and rare mutants of apolipoproteins occur in humans. The polymorphism of apolipoprotein E (apoE) is controlled by three common alleles, epsilon 2, epsilon 3, and epsilon 4, which code for proteins that differ in lipoprotein receptor binding activity, or in their catabolism in vivo, or both. This may explain the observed significant effects of the apoE alleles on the phenotypic variance of plasma lipoprotein concentrations in different ethnic groups and, moreover, the involvement of apoE alleles in the pathogenesis of multifactorial forms of hyperlipidaemia, for example, hypertriglyceridaemia, familial type III hyperlipidaemia (apoE-2 Arg-158----Cys) and polygenic hypercholesterolaemia (apoE-4 Cys-112----Arg). A further polymorphic gene locus controls the concentrations of the Lp(a) lipoprotein complex in plasma, which may vary from less than 1 mg/dl to greater than 200 mg/dl between different individuals. This lipoprotein contains two different polypeptides, apoB-100 and the Lp(a) glycoprotein. The Lp(a) glycoprotein exhibits genetic polymorphism which is controlled by a series of autosomal alleles at a single locus and which is associated with lipoprotein concentrations in plasma. This suggests that the same gene locus is involved in determining Lp(a) glycoprotein phenotypes and Lp(a) lipoprotein concentrations in plasma. Thus, there is evidence that variability in apolipoprotein genes relates to the normal variance of lipoprotein concentrations in the population and that this variability is a major genetic factor in multifactorial forms of hyperlipidaemia.
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PMID:Apolipoproteins, quantitative lipoprotein traits and multifactorial hyperlipidaemia. 296


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