Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several recent reports have examined whether there is a correlation between the presence of some minor alleles of the highly polymorphic apolipoprotein B gene and atherosclerosis and premature heart disease. The present study extends this investigation. A high-resolution method was used to study the allele frequencies of a hypervariable minisatellite region close to the apolipoprotein B gene in 110 patients with severe coronary disease and in 117 normal controls. Alleles containing 38, 44, 46, or 48 hypervariable elements showed an association with coronary heart disease. These alleles were also associated with elevated serum levels of total cholesterol and apolipoprotein B among patients and with elevated serum levels of total triglycerides among controls. The hypervariable region showed strong linkage disequilibrium with a polymorphic EcoRI site in exon 29 and was in linkage equilibrium with a polymorphic MspI site in exon 26. Two patients carried a base change at codon 3500 that results in an arginine-to-glutamine substitution; the base change was linked in both instances to the allele with 48 hypervariable elements.
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PMID:Hypervariability in a minisatellite 3' of the apolipoprotein B gene in patients with coronary heart disease compared with normal controls. 235 70

The plasma concentration of human lipoprotein(a) [Lp(a)] is correlated with the risk of heart disease. A distinct feature of the Lp(a) particle is the apolipoprotein (a) [apo(a)], which is associated with apoB-100, the main protein component of low-density lipoprotein. We now report that apo(a), which has extensive homology to plasminogen, binds to immobilized fibronectin. The binding of Lp(a) was localized to the C-terminal heparin-binding domain of fibronectin. Incubation of Lp(a) with fibronectin resulted in fragmentation of fibronectin. The cleavage pattern, as visualized by gel electrophoresis and immunoblotting, was reproducibly obtained with Lp(a) purified from five different individuals and was distinct from that obtained upon proteolysis of fibronectin by plasmin or kallikrein. The use of synthetic peptide substrates demonstrated that the amino acid specificity for Lp(a) was arginine rather than lysine. The proteolytic activity of Lp(a) was localized to apo(a) and experiments with inhibitors indicated that the proteolytic activity was of serine proteinase-type.
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PMID:Lipoprotein(a) binds to fibronectin and has serine proteinase activity capable of cleaving it. 253 57

Inadequate arginine intake has been suggested as an etiology for hyperammonemia in neonates on parenteral nutrition. We randomized 26 nonasphyxiated neonates to receive amino acid solutions containing either 3.6 or 10.4% of total nitrogen as arginine when intravenous nutrition (IVN) therapy was initiated. Neonates in both amino acid solution study groups were observed to have significantly elevated blood ammonia (BA) concentrations during IVN (p less than 0.01) as compared to pre-IVN levels. Blood ammonia concentrations tended to be higher in infants receiving the 3.6% arginine amino acid solution. Septic infants were at particular risk for hyperammonemia as compared to nonseptic patients (p less than 0.025). Other clinical parameters including birth weight, gestational age, oxygen requirements, enteral nutritional intake, congenital anomalies, and heart disease did not appear to be related to BA concentration.
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PMID:Hyperammonemia in neonates receiving intravenous nutrition. 682 75

Childhood thrombo-embolism is mostly the result of inherited thrombophilia or vascular insults combined with risk factors such as peripartal asphyxia, fetopathia diabetica, exsiccosis, septicaemia, central lines, congenital heart disease, cancer, trauma, surgery or elevated antiphospholipid antibodies. Inherited thrombophilia includes mainly defects of the protein C pathway, resistance to activated protein C, protein C or protein S deficiency. Resistance to activated protein C, in the majority of cases caused by the point mutation Arg 506 Gln of the factor V gene, has emerged as the most important hereditary cause of thrombo-embolism in adults and children. However, since an acquired risk of thrombo-embolic complications frequently masks the inherited deficiency in affected children, children with thrombo-embolism should have adequate laboratory evaluation for inherited coagulation disorders, especially the protein C pathway. Until more data on childhood thrombo-embolism are available, treatment recommendations will continue to be extrapolated from guidelines for adults.
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PMID:Inherited defects of the protein C anticoagulant system in childhood thrombo-embolism. 891 89

Hypertrophic cardiomyopathy is a human heart disease characterized by increased ventricular mass, focal areas of fibrosis, myocyte, and myofibrillar disorganization. This genetically dominant disease can be caused by mutations in any one of several contractile proteins, including beta cardiac myosin heavy chain (beta MHC). To determine whether point mutations in human beta MHC have direct effects on interfering with filament assembly and sarcomeric structure, full-length wild-type and mutant human beta MHC cDNAs were cloned and expressed in primary cultures of neonatal rat ventricular cardiomyocytes (NRC) under conditions that promote myofibrillogenesis. A lysine to arginine change at amino acid 184 in the consensus ATP binding sequence of human beta MHC resulted in abnormal subcellular localization and disrupted both thick and thin filament structure in transfected NRC. Diffuse beta MHC K184R protein appeared to colocalize with actin throughout the myocyte, suggesting a tight interaction of these two proteins. Human beta MHC with S472V mutation assembled normally into thick filaments and did not affect sarcomeric structure. Two mutant myosins previously described as causing human hypertrophic cardiomyopathy, R249Q and R403Q, were competent to assemble into thick filaments producing myofibrils with well defined I bands, A bands, and H zones. Coexpression and detection of wild-type beta MHC and either R249Q or R403Q proteins in the same myocyte showed these proteins are equally able to assemble into the sarcomere and provided no discernible differences in subcellular localization. Thus, human beta MHC R249Q and R403Q mutant proteins were readily incorporated into NRC sarcomeres and did not disrupt myofilament formation. This study indicates that the phenotype of myofibrillar disarray seen in HCM patients which harbor either of these two mutations may not be directly due to the failure of the mutant myosin heavy chain protein to assemble and form normal sarcomeres, but may rather be a secondary effect possibly resulting from the chronic stress of decreased beta MHC function.
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PMID:Point mutations in human beta cardiac myosin heavy chain have differential effects on sarcomeric structure and assembly: an ATP binding site change disrupts both thick and thin filaments, whereas hypertrophic cardiomyopathy mutations display normal assembly. 910 42

The serum concentrations of nitrogen oxides, the stable metabolites of nitric oxide, were measured in 61 children during and after cardiopulmonary bypass (CPB) for surgery of congenital heart disease. Overall, there was a small reduction in serum nitrogen oxide concentrations during CPB, from a median of 27.5 (interquartile range 16.6-55.7) to 26.4 (15.3-40.6) mumol/l, followed by an increase in the following 24 h to 33.1 (21.3-46.7) mumol/l. The largest postoperative increases in nitrogen oxides occurred in children who developed renal impairment, or were treated with nitrovasodilators. There was no relationship between changes in serum nitrogen oxides intraoperatively and early changes in pulmonary vascular resistance, and a weak positive relationship between changes in serum nitrogen oxides and early postoperative changes in cardiac index (r2 = 0.09, p = 0.04). We found no evidence for increased activation of the L-arginine nitric oxide pathway during CPB; and the reduction in nitric oxide metabolites that occurred during CPB were of doubtful significance to pulmonary or systemic haemodynamic changes in the postoperative period.
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PMID:Altered activation of the L-arginine nitric oxide pathway during and after cardiopulmonary bypass. 941 53

Our previous study found that angiotensin-converting enzyme (ACE) inhibitors and amlodipine induce NO release from coronary microvessels through a kinin-dependent mechanism. The goal of this study was to determine whether amlodipine could potentiate NO formation during ACE inhibition. Coronary microvessels were isolated from 16 mongrel dogs. Nitrite, the hydration product of NO, from coronary microvessels was quantified by using the Griess reaction. Bradykinin and kallikrein all significantly increased nitrite release from coronary microvessels in a concentration-dependent manner. The ACE inhibitor, ramiprilat, potentiated these effects. Amlodipine also markedly potentiated nitrite production by ramiprilat. For instance, amlodipine (10(-10) M) enhanced nitrite release induced by ramiprilat (10(-7) M) from 122 +/- 9 to 168 +/- 14 pmol/mg (p < 0.05 vs. ramiprilat). Nitrite release potentiated by ramiprilat and amlodipine was entirely blocked by N(omega)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthase), HOE 140 (Icatibant, a specific B2-kinin receptor antagonist), and dichloroisocoumarin (DCIC, a serine protease inhibitor that blocks local kinin formation). These results clearly show that there is a synergistic effect on NO formation when amlodipine is combined with ACE inhibition. Our data suggest that kinin-mediated coronary NO production may contribute importantly to the beneficial therapeutic action of ACE inhibitors, especially in combination with amlodipine in the treatment of heart disease.
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PMID:Amlodipine enhances NO production induced by an ACE inhibitor through a kinin-mediated mechanism in canine coronary microvessels. 1067 50

A substantial body of evidence suggests involvement of the human beta1-adrenoceptor (beta1-AR) gene in the pathophysiology of dilated cardiomyopathy (DCM), a severe heart disease of significant public health impact. Beta1-AR-mediated signal transduction is dramatically altered due to downregulation, resulting in an impairment of myocardial response. The important role of genetic factors in idiopathic dilated cardiomyopathy (IDCM) recently recognized, we analyzed this prime candidate gene for genetic variation in carefully selected patients and controls. In this preliminary study, 18 single nucleotide polymorphisms were observed, 17 of which were located in the N-terminal and C-terminal region of the coding exon, resulting in 7 amino acid exchanges: Ser-49-Gly, Ala-59-Ser, Gly-389-Arg, Arg-399-Cys, His-402-Arg, Thr-404-Ala, and Pro-418-Ala. These mutations resulted in 11 different beta1-AR genotypes. Importantly, the genotypes carrying the Ser-49-Gly mutation in the N-terminus of the molecule in a heterozygous or homozygous form were observed significantly more frequently in the group of IDCM patients. The present results may provide a clue on the molecular mechanisms involved in IDCM, and add moreover interesting information on nature, distribution, and evolutionary aspects of sequence variation in human adrenergic receptor genes.
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PMID:Beta1-adrenoceptor gene variations: a role in idiopathic dilated cardiomyopathy? 1079 44

Familial defective apolipoprotein B-100 (FDB) R3500Q is an autosomal co-dominant disorder caused by the substitution of glutamine for arginine at amino acid residue 3500 of the apolipoprotein B-100 gene. It is associated with hypercholesterolaemia of varying severity, and with coronary artery disease. Hypercholesterolaemic patients (n = 158) from Northern Ireland were screened for the defect by polymerase chain reaction-mediated, site-directed mutagenesis. Clinical presentation ranged from moderate hypercholesterolaemia with a family history of hypercholesterolaemia or heart disease (n = 104) to those classified as definitely having familial hypercholesterolaemia (FH) (n = 54). Eight (5.1%) unrelated individuals were found to be heterozygous for the FDB R3500Q mutation, including two (3.7%) of those 54 classified clinically as having FH. Treatment with HMG-CoA-reductase-inhibiting drugs (statins) decreased total cholesterol by 22-44% and low-density lipoprotein cholesterol by 34-46% in all but one FDB heterozygote.
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PMID:Familial defective apolipoprotein B-100 (R3500Q) in Northern Ireland. 1079 69

The generation of reactive oxygen species (ROS) is associated with life in aerobic conditions. ROS are thought to be implicated in the pathogenesis of various human diseases since they are capable of damaging biological macromolecules such as DNA, carbohydrates and proteins. The organism maintains defense against ROS, including enzymes and low molecular-weight antioxidants. An important source of antioxidants is diet which contains numerous compounds exhibiting antioxidant activity. A shortage of antioxidants in the diet might promote coronary heart disease through accumulation of oxidized LDL in macrophages. However, antioxidants may also influence endothelial functions, smooth muscle cell proliferation, thrombosis and plaque rupture. Consumption of fruits and vegetables, olive oil, red wine and tea is inversely correlated with heart disease rates. These foods are particularly rich in natural antioxidant nutrients, including ascorbate (vitamin C), the tocopherols (vitamin E) and carotenoids. More than 600 naturally occurring carotenoids have been identified. These compounds are plant pigments that provide the bright color of various fruits and vegetables; lycopene, which gives tomatoes their red color, is under active research. Flavonoids are > 4,000 naturally occurring substances which provide color, texture and taste for plant foods. As free radical scavengers, flavonoids inhibit lipid peroxidation, promote vascular relaxation and help prevent atherosclerosis. A sufficient supply with antioxidants from diet might help prevent or delay the occurrence of pathological changes associated with oxidative stress. When diet fails to meet the antioxidant requirement, dietary supplements might be indicated. The recently coined term nutriceuticals describes a variety of nonprescription products that are used to enhance health. The best known are vitamin E, vitamin C, carotenoids, coenzyme Q10, flavonoids and the amino acid L-arginine. Rigorous clinical trials, particularly among high-risk groups, are needed before they can be recommended routinely to patients.
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PMID:Dietary antioxidants for cardiovascular prevention. 1081 86


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