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)

The importance of metals in normal and pathologic cardiovascular function has been recognized. Significant derangements in myocardial Ca2+, Mg2+, and Cu2+ have been reported in ischemic heart injury. We studied 3 groups of hearts: 1) fifteen specimens obtained from patients who had no heart disease, 2) nine specimens from patients who had expired from cyanotic congenital heart disease, and 3) ten specimens from patients who had expired from acute rheumatic heart disease with carditis and severe heart failure. None of the patients had undergone cardiac surgery. Left ventricular lateral wall Mg2+, Ca2+, Cu2+, and Zn2+ contents were measured by atomic absorption spectrometry. The results showed a significant decrease in myocardial Mg2- (Group I 177.06 +/- 32.71; Group II 155.66 +/- 14.79; Group III 149.00 +/- 13.29, p less than 0.05 and p less than 0.01, respectively), and Cu2+ contents (Group I 3.22 +/- 0.37; Group II 2.94 +/- 0.22; Group III 2.56 +/- 0.32, p less than 0.02 and p less than 0.001, respectively), and a rise in myocardial Ca2+ content (Group I 36.06 +/- 10.72; Group II 43.22 +/- 7.01; Group III 46.30 +/- 4.85, p = not significant, and p less than 0.01, respectively). The myocardial Zn2+ content did not change significantly (Group I 26.53 +/- 3.99; Group II 26.00 +/- 4.15; Group III 26.40 +/- 3.53). The myocardial Mg2+/Ca2+ ratio was reduced markedly in both groups (Group I 5.328 +/- 1.879; Group II 3.685 +/- 0.735; Group III 3.135 +/- 0.291, p less than 0.001 for both Groups II and III vs Group I). The latter results correlated closely with the myocardial Mg2+/Ca2+ ratios reported in experimental models in peri-infarction zones. Thus, the myocardium of patients who had expired from cyanotic congenital heart disease and acute rheumatic carditis is jeopardized by ischemia, with metal contents similar to the border areas in myocardial infarction.
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PMID:Myocardial metal content in patients who expired from cyanotic congenital heart disease and acute rheumatic heart disease. 717 80

Children with congenital heart disease may have significant growth retardation, which in part may be caused by insufficient dietary intake. Data on energy and nutrient intake were collected using a 14-day dietary record by weighing, in 22 children with congenital heart disease (mean age 39 months, range 12-126 months), prior to corrective operation. When viewed in relation to actual weight, energy intake averaged 88% (SD 17%) of that recommended by the FAO/WHO/UNU. Energy intakes and weight SD scores were significantly correlated (r = 0.55, p < 0.01). Protein intake was generally high, and even sufficient to allow catch-up growth. The majority of the children did not meet the recommendations for iron, zinc, calcium, or vitamins D, E, C, B1 or B6. Parents should be advised to give their children vitamin/mineral supplements, and to supply extra energy to children with failure to thrive.
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PMID:Energy and nutrient intakes in congenital heart disease. 847 62

The endocrine phase of the stress response to cardiopulmonary bypass in children is known to be subtly different from that seen in adults. The aim of this investigation was to determine whether there are similar differences in the acute phase response. Thirteen children were studied (mean age 2.65 years). Each child had congenital heart disease and underwent corrective cardiac surgery. Blood samples taken two days prior to operation and at 6, 9, 12, 24, 48 and 120 hours after were analysed for C-reactive protein, albumin, caeruloplasmin, zinc and copper concentrations. Metal:carrier protein molar ratios were also calculated. Results demonstrate changes which, although similar to those seen in adults, differed both quantitatively and qualitatively. This is explained by the concept of immaturity leading to a generally poor capacity for protein synthesis and a relative inability to respond to altered circumstances.
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PMID:The acute phase response to cardiopulmonary bypass in children. 874 Mar 51

A single cross-sectional study for serum copper and zinc levels was evaluated in 20 patients with cancer (respiratory, digestive, haematological, gynaecological) and 21 patients with cardiopathy (acute myocardial infarction and ischemic cardiomyopathy). A control group of 84 healthy subjects was selected. The mean serum zinc levels in patients with gynaecological cancer and ischemic cardiomyopathy were significantly lower than the control group (P < 0.05). However, the mean serum copper level was not statistically different among patients with cancer (P < 0.05) and cardiomyopathy (P > 0.05) than the control group. Male patients did not have statistically different values for serum Cu (P > 0.05) and Zn (P < 0.05) than those found in female patients. Patients' age did not have any statistical influence (P > 0.05) on serum Cu and Zn levels.
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PMID:Serum copper and zinc concentrations in serum from patients with cancer and cardiovascular disease. 929 67

Tricuspid atresia (TA) is a common form of congenital heart disease, accounting for 1-3% of congenital cardiac disorders. TA is characterized by the congenital agenesis of the tricuspid valve connecting the right atrium to the right ventricle and both an atrial septal defect (ASD) and a ventricular septal defect (VSD). Some patients also have pulmonic stenosis, persistence of a left-sided superior vena cava or transposition of the great arteries. Most cases of TA are sporadic, but familial occurrences with disease in multiple siblings have been reported. Gata4 is a zinc-finger transcription factor with a role in early cardiac development. Gata4-deficient mice fail to form a ventral heart tube and die of circulatory failure at embryonic day (E) 8.5 (refs 6,7). Zfpm2 (also known as Fog-2) is a multi-zinc-finger protein that is co-expressed with Gata4 in the developing heart beginning at E8.5 (refs 8-10). Zfpm2 interacts specifically with the N-terminal zinc finger of Gata4 and represses Gata4-dependent transcription. Here we use targeted mutagenesis to explore the role of Zfpm2 in normal cardiac development. Zfpm2-deficient mice died of congestive heart failure at E13 with a syndrome of tricuspid atresia that includes an absent tricuspid valve, a large ASD, a VSD, an elongated left ventricular outflow tract, rightward displacement of the aortic valve and pulmonic stenosis. These mice also display hypoplasia of the compact zone of the left ventricle. Our findings indicate the importance of Zfpm2 in the normal looping and septation of the heart and suggest a genetic basis for the syndrome of tricuspid atresia.
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PMID:A syndrome of tricuspid atresia in mice with a targeted mutation of the gene encoding Fog-2. 1088 89

Methyl mercury (MeHg) has been shown to change Coxsackie virus type B3 (CB3) myocarditis in a direction compatible with the development of chronic disease. Murine models of CB3 myocarditis closely mimic the pathogenesis in humans. There are also indications that metals, such as mercury, and trace elements may interact and adversely affect viral replication and development of inflammatory lesions. The effects of low-dose MeHg exposure on myocardial trace element distribution, as determined by means of nuclear microscopy, was studied in CB3 myocarditis. Balb/c mice were fed a MeHg-containing diet (3.9 mg/kg diet) for 12 wk prior to infection. Areas of inflammatory lesions in the myocardium were identified by traditional histologic examination, and serial tissue sections in these selected areas were used for immune histology (macrophages), in situ hybridization of virus genomes, and nuclear microscopy of tissue trace element distribution. Areas with no inflammation or virus were compared with areas of ongoing inflammation and viral replication. In the inflammatory lesions of MeHg-exposed mice as compared to nonexposed mice, the myocardial contents of calcium (Ca), manganese (Mn), and iron (Fe) were significantly increased, whereas the zinc (Zn) content was decreased. The increased Ca and decreased Zn contents in the inflamed heart may partly explain a more severe disease in MeHg-exposed individuals. Although not significant in the present study, with a limited number of mice, the inflammatory and necrotic lesions in the ventricular myocardium on d 7 of the infection was increased by 50% (from 2.2% to 3.3% of the tissue section area) in MeHg-exposed mice and, also, there was a tendency of increased persistence of virus with MeHg exposure. No increased MeHg uptake, either in the inflammatory lesions or in the areas of noninflamed heart tissue in infected mice, could be detected. The present results indicate that a "competition" exists between potentially toxic heavy metals from the environment/diet and important trace elements in the body and that a disturbed trace element balance adversely influences the development of pathophysiologic changes in inflammatory heart disease.
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PMID:Trace element distribution in heart tissue sections studied by nuclear microscopy is changed in Coxsackie virus B3 myocarditis in methyl mercury-exposed mice. 1131 73

Sudden Unexplained Death Syndrome (SUDS) is a major health problem in rural residents of Northeast Thailand. The cause of death in SUDS is suspected to be cardiovascular abnormalities. As magnesium (Mg) and zinc (Zn) deficiency contribute significantly to several cardiovascular diseases, we investigated the Mg- and Zn-status of patients with sudden respiratory distress and cardiac arrest who had survived resuscitation attempts or a near-SUDS episode (N-SUDS). The following subjects were enrolled: 12 N-SUDS inhabitants of rural Northeast Thailand (rural group 1, R1), 13 rural villagers with no past history of N-SUDS (rural group 2, R2), 15 urban Northeasterners (urban group 1, U1); 13 Bangkokians (urban group 2, U2). All subjects were free of structural heart disease. Magnesium and zinc were assessed by atomic absorption spectrophotometry of samples of plasma, red blood cells (RBC), white blood cells (WBC), and 24-hour urine. The mean levels of magnesium in the RBC, WBC, and 24-hour urine of N-SUDS patients (R1) were significantly lower than those of the urban groups (U1 and U2), while the plasma levels did not show any differences. When comparing the Zn-status of R1 with that of the urban groups (U1 and U2), the plasma, RBC, and WBC levels were found to be significantly lower in R1 (except for the RBC-Zn of the U1 group), while the 24-hour urine levels was higher. Although the magnesium and zinc parameters were not significantly different between the rural groups R1 and R2, the prevalence of hypomagnesuria (<2.2 mmol/day), hypozincemia (<9.7 micromol/l), and hyperzincuria (>10.7 micromol/day) was higher in the R1 group. These findings suggest that the homeostasis of both magnesium and zinc is altered in N-SUDS patients. Similar alterations, to a lesser degree, were observed in those people living in the same rural environment (R2).
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PMID:Magnesium and zinc status in survivors of sudden unexplained death syndrome in northeast Thailand. 1211 48

The development of the complex network of specialized cells that form the atrioventricular conduction system (AVCS) during cardiac morphogenesis occurs by progressive recruitment within a multipotent cardiomyogenic lineage. Understanding the molecular control of this developmental process has been the focus of recent research. Transcription factors representative of multiple subfamilies have been identified and include members of zinc-finger subfamilies (GATA4, GATA6 HF-1b), skeletal muscle transcription factors (MyoD), T-box genes (Tbx5), and also homeodomain transcription factors (Msx2 and Nkx2.5). Mutations in some of these transcription factors cause congenital heart disease and are associated with cardiac abnormalities, including deficits within the AVCS. Mouse models that closely phenocopy known human heart disease provide powerful tools for the study of molecular effectors of AVCS development. Indeed, investigations of the Nkx2.5 haploinsufficient mouse have shown that peripheral Purkinje fibers are significantly underrepresented. This piece of data corroborates our previous work showing in chick, mouse, and humans that Nkx2.5 is elevated in the differentiating AVCS relative to adjacent working ventricular myocardial tissues. Using the chick embryo as a model, we show that this elevation of Nkx2.5 is transient in the network of conduction cells comprising the peripheral Purkinje fiber system. Functional studies using defective adenoviral constructs, which disrupt the normal variation in level of this gene, result in perturbations of Purkinje fiber phenotype. Thus, the precise spatiotemporal regulation of Nkx2.5 levels during development may be required for the progressive emergence of gene expression patterns specific to differentiated Purkinje fiber cells.
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PMID:Transcriptional regulation of cardiac conduction system development: 2004 FASEB cardiac conduction system minimeeting, Washington, DC. 1536 44

The zinc-dependent enzymes known as matrix metalloproteinases (MMPs) are medicinal targets due to the activity of these enzymes associated with diseases such as cancer, heart disease, and arthritis. The development of most MMP inhibitors (MPIs) has followed a basic design formula: a peptidomimetic backbone is attached to a zinc-binding group (ZBG). MPI backbones have varied enormously and improved with increased knowledge of MMP structure and function while hydroxamic acids have been used as the ZBG in most inhibitors. The problems associated with hydroxamic acid and other current ZBGs have been identified; the incorporation of more potent and selective ZBGs for the active site zinc(II) ion is necessary to improve the development of second-generation inhibitors. Herein, we highlight ZBGs that have been proposed as alternatives to hydroxamic acids. In addition, techniques used to identify new ZBGs are also discussed. New insights from a bioinorganic approach using model complexes of the MMP active site are presented as tools in examining the mode of binding for various known and novel ZBGs. Novel computational methods are highlighted that allow for modeling the drug-protein interactions with non-hydroxamate inhibitors of MMPs. We suggest that significant efforts to augment ZBGs combined with the available information on inhibitor backbone design will accelerate the discovery of improved MPIs. Newly devised drug design methods will help to realize this proposal.
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PMID:A bioinorganic perspective on matrix metalloproteinase inhibition. 1557 96

The Marshall-Smith syndrome (MSS) is rare congenital disorder, characterized by a triad of orofacial dysmorphism, failure to thrive, and accelerated osseous maturation. An 8-year-old boy with MSS associated with congenital glaucoma, corneal erosion, laryngomalacia, glossoptosis, choanal stenoses, bilateral peripheral hearing defect, ventriculomegaly, congenital heart disease (atrial septal defect), chronic pulmonary disease, and scoliosis was reported. A tracheostomy with endotracheal tube insertion was performed for his difficult airway. He has longer survival time than those MSS patients hitherto reported. High-resolution chromosome banding and extensive metabolic investigation did not detect any abnormality, except for low blood levels of zinc and thyroxine. Besides, brain atrophy with hypoplastic cerebellum and brainstem, and bilateral hydronephrosis with hydroureter were detected by image studies.
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PMID:Long-term follow-up of Marshall-Smith syndrome: report of one case. 1562 71


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