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)

Arginine decreased cholesterol and triglyceride content in blood sera of intact rats and inhibited the development of hyperlipidemia provoked by Triton WR-1339 injection. In rabbits pretreated with cholesterol arginine diminished the content of blood serum cholesterol and triglycerides. Introduction of arginine to intact and hyperlipidemic guinea pigs decreased the VLDL and increased the HDL level. Under influence of arginine electrophoretic zone of HDL apo A-1 was more pronounced and apo E zone became less distinct in hyperlipidemic guinea pigs.
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PMID:[Effect of arginine on the lipid and lipoprotein content of animal blood]. 652 39

Resistance to both insulin and glucagon have been considered as possible causes of primary hypertriglyceridemia. In the present research, we have compared insulin and glucagon secretion in five hyperlipidemic patients with familial dysbetalipoproteinemia with five normolipidemic control subjects matched for age, sex and adiposioty. Plasma insulin and glucagon concentrations mesaured during standard oral glucose tolerance and arginine infusion tests were similar in the two groups. Blood glucose fell transiently in the controls, but not in the patients, during the Himsworth test (100 g glucose orally plus 0.05 U insulin per kg body weight intravenously). There were no significant differences in plasma FFA concentrations and responses during all tests between the groups. The percentage reduction in plasma triglyceride concentration during infusion of arginine was similar in the two groups. These results suggest that the patients with familial dysbetalipoproteinemia were slightly less insulin sensitive than the controls. However, primary insensitivity to glucagon or insulin does not appear to be fundamental to the pathogenesis of hyperlipidemia in familial dysbetalipoproteinemia.
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PMID:Pancreatic alpha and beta cell function in familial dysbetalipoproteinemia. 700 Jun 52

Recent work in our laboratory has shown that oral administration of triphenyltin fluoride (TPTF) evokes hypertriglyceridemia in rabbits. The present experiments were conducted to elucidate the mechanism of TPTF-induced hypertriglyceridemia in rabbits by a combined biochemical and ultrastructural approach. After a single TPTF administration, fasting blood glucose and plasma triglyceride levels increased significantly (P less than 0.02) for about 20 days. On the other hand, both plasma and adipose tissue lipoprotein lipase (LPL) activity was markedly decreased (P less than 0.001) during this period, and triglyceride production rates on day 2 after TPTF administration was significantly decreased (P less than 0.01). Density-gradient ultracentrifugation showed a remarkable accumulation of chylomicron and VLDL in the composition of plasma lipoproteins. Insulin injection to the hypertriglyceridemic rabbits induced a significant recovery of the decreased plasma LPL activity with a concomitant decrease of plasma triglyceride levels, while abeyance of insulin injection resulted in a decrease of LPL activity again. A significant inhibition of insulin release in response to the loading of glucose, glucagon, or arginine was observed in the TPTF rabbits (P less than 0.02). Inhibition of glucagon release was also observed in the arginine-loading test (P less than 0.01). Electron microscopic studies showed small abnormalities in the pancreatic islets of TPTF-treated rabbits. These findings suggest that TPTF inhibits insulin release from rabbit islets, subsequently inducing diabetic lipemia due to the insulin deficiency. Furthermore, it is possible to provide a new animal model for diabetes and diabetic lipemia by administration of TPTF to rabbits.
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PMID:Triphenyltin fluoride (TPTF) as a diabetogenic agent. TPTF induces diabetic lipemia by inhibiting insulin secretion from morphologically intact rabbit B-cell. 703 Aug 27

Hyperlipidemia contributes to the development of intimal hyperplasia and subsequent accelerated atherosclerosis in vein bypass grafts. This study examines the effect of dietary supplementation with L-arginine on the development of intimal hyperplasia and the vasomotor function of vein grafts in hypercholesterolemic animals. Thirty male New Zealand White rabbits had a right carotid vein bypass graft and were sacrificed at 28 days postoperatively. Twenty animals received a 1% cholesterol diet for 4 weeks prior to surgery and this diet was continued until harvest. Of these, 10 also received L-arginine (2.25%, 2 g/kg, p.o.) 7 days preoperatively and thereafter until harvest. The last 10 animals were controls. Vein grafts were harvested either for morphology or for in vitro isometric tension studies. Cumulative dose-response curves to norepinephrine, serotonin, and bradykinin were recorded, and following norepinephrine precontraction, relaxation to acetylcholine and sodium nitroprusside were determined. After in situ pressure fixation, intimal thicknesses of the vein grafts were measured by videomorphometry. The addition of L-arginine doubled the serum arginine concentrations. Intimal hyperplasia of both groups of hypercholesterolemic vein grafts contained foam cells and lipid-laden endothelial and smooth muscle cells. There was a 24% reduction in the intimal thickness of vein graft intimal hyperplasia in the L-arginine group compared to that in the hypercholesterolemia group (P < 0.05). All hypercholesterolemic vein grafts were two-fold thicker than in the control group. L-arginine supplementation resulted in the preservation of acetylcholine-mediated relaxation but did not change hypercholesterolemia-induced contractile agonist supersensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Control of accelerated vein graft atheroma with the nitric oxide precursor: L-arginine. 763 Jan 34

Common variants at the apolipoprotein B gene locus are associated with hyperlipidaemia, but conflicting data have been presented in the literature concerning the size of the effects and which polymorphisms give the best signal in the different groups of individuals studied. In this review, we will present a critique on the use and interpretation of association studies, with respect to the recent apolipoprotein B DNA polymorphism studies. The impact of these common polymorphisms and rare mutations of apolipoprotein B, primarily the substitution of arginine by glutamine at residue 3500 (R3500Q) that causes familial defective apolipoprotein B100, will also be considered.
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PMID:Hyperlipidaemia associated with genetic variation in the apolipoprotein B gene. 767 Jul 50

Prothrombin fragment 1.2 (F1.2) is an activation peptide generated during a critical event of blood coagulation, the conversion of prothrombin to thrombin. As a marker of thrombin generation, F1.2 has clinical potential in assessing thrombotic risk and monitoring anticoagulant therapy. In developing a highly specific, monoclonal antibody-based immunoassay of human plasma F1.2, we generated six murine anti-F1.2 monoclonal antibodies, using as immunogen a synthetic peptide (sequence: CGSD-RAIEGR) similar to the unique carboxyl terminus of F1.2. Each antibody bound F1.2 but not prothrombin. Epitope mapping studies with one antibody (5-3B) showed that optimum binding required six to eight amino acids plus a terminal arginine to emulate the F1.2 carboxyl terminus. A quantitative sandwich ELISA for human plasma F1.2 was configured with monoclonal antibody 5-3B as the capture antibody and peroxidase-labeled polyclonal antibodies to the F1.2 amino-terminal region as detector antibodies. Calibrators were prepared by adding purified F1.2, 0-10 nmol/L, to F1.2-depleted plasma. Assay characteristics included the following: mean (+/- SD) analytical recovery of 98% +/- 13%; no interference from lipemia, hemolysis, icterus, or thrombolytic agents; 0.08 nmol/L sensitivity; and mean intra- and interassay imprecision (three lots) < 12% at both low and high concentrations of F1.2.
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PMID:Monoclonal antibodies specific for prothrombin fragment 1.2 and their use in a quantitative enzyme-linked immunosorbent assay. 847 48

Apolipoprotein (apo) E mediates the removal of chylomicron and VLDL remnants from plasma. In a proband with mild hyperlipidemia and a family history of premature coronary artery disease, we have identified a new mutant of apoE with an isoelectric point close to but distinct from that of apoE3. Sequencing of the apoE gene from this subject (JB) revealed that the subject was heterozygous for a G to A substitution in codon 136, resulting in the substitution of histidine for arginine; therefore, we have designated this isoform apoE3' (Arg136-->His). Examination of the proband's kindred revealed that the nine carriers (all heterozygotes) of the variant isoform displayed a twofold elevation in the concentration of very low density lipoprotein (VLDL) cholesterol (40 +/- 8 mg/dl) and triglyceride (109 +/- 19) compared to the nine noncarriers (19 +/- 3 and 55 +/- 13, respectively). In all carriers, the VLDL displayed an abnormal double pre-beta pattern upon electrophoresis. The low density lipoprotein receptor-binding activity of purified apoE3' (Arg136-->His) when complexed with DMPC was slightly defective (80% of the activity of normal apoE). The mutant apoE also displayed a reduced affinity for heparin compared to apoE3. As both of these biochemical parameters are known to be important in VLDL clearance, the defects associated with this variant are likely responsible for the increase in VLDL observed in carriers. None of the carriers displayed clinical features of type III hyperlipoproteinemia, suggesting that the relatively mild dyslipoproteinemic phenotype associated with this variant might be associated with recessive expression of this disorder. However, the abnormal VLDL phenotype appears to be dominantly expressed.
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PMID:Identification and characterization of a novel apolipoprotein E variant, apolipoprotein E3' (Arg136-->His): association with mild dyslipidemia and double pre-beta very low density lipoproteins. 770 48

A new rare apolipoprotein E mutant was identified as we were investigating the apolipoprotein E genotype of patients with type III hyperlipidemia (HLP III). The unusual DNA restriction fragment length polymorphism profile and then the sequence analysis of a PCR amplified fragment of the proband's apo E gene revealed a simple base substitution (G-->T) at nucleotide 3836. This mutation leads to the replacement of arginine by leucine at position 142 of the mature protein. The proband carried the mutant allele at the heterozygous status with an epsilon 3 allele. Subsequently, analysis of the proband's father's apo E gene showed that same mutated allele associated with an epsilon 2 allele. The two subjects presented a dysbetalipoproteinemia in which this new apo E variant could be implicated.
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PMID:Identification of a new apolipoprotein E variant (E2 Arg142-->Leu) in type III hyperlipidemia. 777 63

While determining the apolipoprotein-E (apo-E) genotype of 22 patients with type III hyperlipidemia (HLP III) by restriction isotyping, we identified a new mutant form of apo-E by its unusual DNA restriction fragment length polymorphism pattern. DNA sequence analysis of a polymerase chain reaction-amplified portion of the proband's apo-E gene revealed the substitution of cysteine (TGC) for arginine (CGC) at position 136 in the mutant allele (designated R136C). Lipoproteins containing this mutant protein bound defectively to macrophages in vitro, confirming the contribution of R136C to the expression of HLP III in the proband. The proband's two siblings carried the mutant allele and were also heterozygous for E2. Each also had dysbetalipoproteinemia (indicated by the presence of beta-very low density lipoprotein), but neither was hyperlipidemic, attesting to the importance of other factors for the full expression of HLP III. The mutant allele appears to contribute to the inheritance of HLP III in a recessive fashion. Restriction isotyping facilitates the diagnosis of subjects with HLP III, aids in the identification of affected individuals through family screening, and can contribute to the discovery of new mutations that help explain the pathogenesis of HLP III.
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PMID:Detection of a new apolipoprotein-E mutation in type III hyperlipidemia using deoxyribonucleic acid restriction isotyping. 790 41

Transgenic mice were prepared that expressed a dysfunctional apo E variant, apo E (Arg-112, Cys-142), which is associated with dominant inheritance of type III hyperlipoproteinemia (type III HLP) in humans. Among eight founder mice, plasma apo E (Arg-112, Cys-142) levels varied 100-fold and directly correlated with plasma cholesterol and triglyceride levels. On a normal chow diet, mice expressing high levels (> 70 mg/dl) of the dysfunctional apo E had grossly elevated plasma lipids, with cholesterol levels of up to 410 mg/dl and triglyceride levels of up to 1,210 mg/dl. Upon agarose electrophoresis, plasma from these mice demonstrated beta-very low density lipoproteins (beta-VLDL). Mice expressing low (< 2.5 mg/dl) or intermediate (21 mg/dl) levels of the apo E variant had much less severe hyperlipidemia and did not have beta-VLDL. Although the transgenic mouse beta-VLDL were enriched in cholesteryl esters compared with normal mouse VLDL, they were not as cholesterol enriched as human beta-VLDL from type III HLP subjects. Transgenic mouse beta-VLDL injected into normal mice were cleared from plasma at a significantly slower rate than normal mouse VLDL, demonstrating the impaired catabolism of beta-VLDL. Thus, transgenic mice expressing high levels of the dysfunctional apo E (Arg-112, Cys-142) variant have many characteristics of the human type III HLP phenotype and appear to be a suitable animal model for this disorder.
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PMID:Type III hyperlipoproteinemic phenotype in transgenic mice expressing dysfunctional apolipoprotein E. 837 2


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