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)

Expression of Cardiac Cytokines and Inducible Form of Nitric Oxide Synthase (NOS2) in Trypanosoma cruzi-infected Mice. Journal of Molecular and Cellular Cardiology (1999) 31, 75-88. Both cardiac cytokine and inducible nitric oxide synthase (NOS2) expression have been implicated in the cardiac dysfunction associated with myocarditis and cardiomyopathy. Chagas' disease, caused by Trypanosoma cruzi, is an important cause of cardiomyopathy. We examined the effect of T. cruzi (Brazil strain) infection with or without verapamil treatment on the expression of cytokines and NOS2 in the heart. Messenger RNA for NOS2, IL-1beta, and TNF-alpha was induced in the myocardium of infected mice, and Western blot analysis as well as immunohistochemistry demonstrated a significant increase in NOS2 protein. Verapamil treatment reduced the expression of cardiac NOS2 protein and the mRNAs for NOS2, TNF-alpha, and IL-1beta. Infection-associated increases in cardiac L-citrulline were also reduced by verapamil treatment. Verapamil-treated infected mice that survived for 80 days exhibited less inflammation and fibrosis compared to untreated mice. Gated MRI and echocardiography revealed an increased right ventricular inner diameter (RVID) in untreated but not in verapamil-treated infected CD1 mice. This suggests that the infection-associated expression of cytokines and NOS2 in the heart correlate with the severity of myocarditis and the effect of verapamil. The RVID was significantly increased in infected wild-type (WT) compared to infected syngeneic NOS2 knockout (NOS2-/-) mice. Fractional shortening was decreased and myocardial L-citrulline was increased in infected WT mice. These data suggest that NO generated from cardiac NOS2 may participate in the pathogenesis of murine chagasic heart disease.
J Mol Cell Cardiol 1999 Jan
PMID:Expression of cardiac cytokines and inducible form of nitric oxide synthase (NOS2) in Trypanosoma cruzi-infected mice. 1007 17

The DiGeorge syndrome (DGS) is a developmental defect of the third and fourth pharyngeal pouches, which is associated with congenital heart defects, hypoparathyroidism, cell-mediated immunodeficiency, velo-pharyngeal insufficiency and craniofacial dysmorphism. The aetiological factor in a great majority of DGS cases is monosomy for the chromosomal region 22q11. To analyze DGS at the molecular level, a new molecular probe (DGCR680) encompassing the ADU balanced translocation breakpoint was prepared. When 13 Korean patients with DGS-type congenital heart disease were analyzed with this probe, 9 turned out to have a deletion at this locus, and all of them except one exhibited a typical facial dysmorphism associated DGS. Though only 9 independent patients were detected to have a deletion at the locus using the commercial probe N25 (D22S75), which maps at about 160 kb from the ADU breakpoint to the telomeric end, results from fluorescence in situ hybridization revealed a deletion in all cases tested at this locus. Two patients who had a deletion at the locus D22S75 but not at DGCR680 did not exhibit any DGS-type facial abnormalities. This result implies that the 680 bp probe covering the ADU translocation breakpoint might be a candidate for a molecular marker that can distinguish a specific phenotype, such as facial features associated with the DiGeorge syndrome. This study also suggested that systematic approaches with several small DNA probes along the DGCR could help to dissect the complex phenotypes associated with the DiGeorge syndrome, such as cardiac defects, abnormal faces, thymic hypoplasia, cleft palate, and hypocalcemia, etc.
Mol Cells 1999 Feb 28
PMID:Molecular genetic analysis of the DiGeorge syndrome among Korean patients with congenital heart disease. 1010 75

In a study of a group of elderly athletes we observed an unexpected association between serum cholesterol levels and the HTTLPR insertion/deletion polymorphism of the promoter region of the serotonin transporter gene (HTT, SLC6A4). As a follow-up we examined the potential association of this polymorphism with cholesterol and triglyceride levels, or heart disease, in two other groups of subjects. We examined the possible association between cholesterol levels and heart disease and genotypes of the HTTLPR insertion/deletion polymorphism of the promoter region of the HTT gene, in three independent study populations ranging from 42 to 90 years of age. For subjects 55 to 70 years of age in Group 1, cholesterol levels were significantly greater in the LS heterozygotes than either LL or SS homozygotes, indicating a heterosis effect (P </= 0.0001). This was replicated in Group 2 (P </= 0.015). Triglyceride levels were also significantly elevated in the LS subjects (P </= 0.001). In Groups 1 and 3 there was a significant association between LS heterozygosity and heart disease, angina, and heart attacks in subjects 70 years of age or less. All of these associations were absent in subjects >70 years of age. While these studies are preliminary and exploratory, they are consistent with a relationship of the HTT gene in cholesterol levels and a risk for heart disease. Replication of these findings in independent, epidemiologically based studies is required.
Mol Genet Metab 1999 Jul
PMID:Association of the serotonin transporter gene with serum cholesterol levels and heart disease. 1038 32

The Enterovirus may be the most common agent responsible for viral myocarditis and cardiomyopathy. Very little of the literature is available concerning the follow-up of patients who underwent transplantation with enteroviral positivity in native hearts. In the present study, 45 explanted hearts from patients who underwent orthotopic heart transplant at University of Padova were studied by reverse transcriptase (RT)-polymerase chain reaction (PCR): 27 patients had dilated cardiomyopathy (DC), 12 had ischemic cardiopathy (IC), 2 had valvular disease (VD), 2 had arrhythmogenic right ventricular cardiomyopathy (ARVC), 1 had giant cell myocarditis (GCM), and 1 had lymphocytic myocarditis (LM). Two sets of PCR primers from the highly conserved region of Enterovirus and Rhinovirus were used. Samples of both ventricles and septum were analyzed in every patients. The RT-PCR and nucleotide sequencing of amplicons were also performed on all post-transplantation follow-up biopsies in patients with Enterovirus positivity in the native heart. The viral genome was detectable in only 1 of 27 patients with DC (3%) and in 1 patient with LM. Nucleotide sequence analysis of the amplified product showed differences in nucleotide sequence of PCR samples compared with the sequence of the coxsackievirus B3 used in the current study. The patient with Enterovirus-positive DC showed a higher index of severe rejection (>3A) in the first 6 months, compared with the other patients tested. The patient with Enterovirus-positive LM died of disease recurrence 2 months after transplantation. The present study reveals a scarce presence of Enterovirus in the myocardium of patients with chronic myocardial disease. Because Enterovirus infection was predictive of a poor prognosis in these two patients, molecular studies are useful in excluding viral involvement in native hearts of transplanted patients.
Diagn Mol Pathol 1999 Mar
PMID:Enteroviral genome in native hearts may influence outcome of patients who undergo cardiac transplantation. 1040 92

The isoprenoid metabolic pathway is mainly regulated at the level of conversion of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) to mevalonate, catalyzed by HMG CoA reductase. As estrogens are known to influence cholesterol metabolism, we have explored the potential regulation of the HMG CoA reductase gene promoter by estrogens. The promoter contains an estrogen-responsive element-like sequence at position -93 (termed Red-ERE), which differs from the ERE consensus by one mismatch in each half of the palindrome. A Red-ERE oligonucleotide specifically bound estrogen receptor in vitro and conferred receptor-dependent estrogen responsiveness to a heterologous promoter in all cell lines tested. However, expression of a reporter driven by the rat HMG CoA reductase promoter was induced by estrogen treatment after transient transfection into the breast cancer cell line MCF-7 cells but not in hepatic cell lines expressing estrogen receptor. Estrogen induction in MCF-7 cells was dependent on the Red-ERE and was strongly inhibited by the antiestrogen ICI 164,384. A functional cAMP-responsive element is located immediately upstream of the Red-ERE, but cAMP and estrogens inhibit each other in terms of transactivation of the promoter. Similarly, induction by estrogens was inhibited by micromolar concentrations of cholesterol, likely acting via changes in occupancy of the sterol-responsive element located 70 bp upstream of the Red-ERE. Thus, within its natural context, Red-ERE is able to mediate hormonal regulation of the HMG CoA reductase gene in tissues that respond to estrogens with enhanced cell proliferation, while it is not operative in liver cells. We postulate that this tissue-specific regulation of HMG CoA reductase by estrogens could partially explain the protective effect of estrogens against heart disease.
Mol Endocrinol 1999 Aug
PMID:The promoter of the rat 3-hydroxy-3-methylglutaryl coenzyme A reductase gene contains a tissue-specific estrogen-responsive region. 1044 99

Heart disease is one of the major cause of death in diabetic patients, but the pathogenesis of diabetic cardio-myopathy remains unclear. In this experiment, to assess the significance of G protein signaling pathways in the pathogenesis of diabetic cardiomyopathy, we analyzed the expression of G proteins and the activities of second messenger dependent protein kinases: cAMP-dependent protein kinase (PKA), DAG-mediated protein kinase C (PKC), and calmodulin dependent protein kinase II (CaM kinase II) in the streptozotocin induced diabetic rat heart. The expression of Galphaq was increased by slightly over 10% (P<0.05) in diabetic rat heart, while Galphas, Galphai, and Gbeta remained unchanged. The PKA activity in the heart did not change significantly but increased by 27% (P<0.01) in the liver. Insulin treatment did not restore the increased activity in the liver. Total PKC activity in the heart was increased by 56% (P<0.01), and insulin treatment did not restore such increase. The CaM kinase II activity in the heart remained at the same level but was slightly increased in the liver (14% increase, P<0.05). These findings of increased expression of Galphaq in the streptozotocin-diabetic rat heart that are reflected by the increased level of PKC activity and insensitivity to insulin demonstrate that alteration of Galphaq may underlie, at least partly, the cardiac dysfunction that is associated with diabetes.
Exp Mol Med 1999 Dec 31
PMID:Increased expression of Galphaq protein in the heart of streptozotocin-induced diabetic rats. 1063 Mar 71

Heart disease remains one of the leading causes of morbidity and mortality in the industrialized nations of the world. Intense investigation has centered around identifying and manipulating intracellular signaling pathways that direct hypertrophic and myopathic responses in an attempt to intervene in the progression or reverse certain forms of heart disease. We show here that cyclosporin A-mediated inhibition of the calcium-regulated phosphatase, calcineurin (PP2B), reverses cardiac hypertrophy and myopathic dilation in two transgenic mouse models of cardiomyopathy. Reversal was demonstrated by gravimetric analysis, echocardiography, histological analysis, and molecular analysis of hypertrophy-associated gene expression. In contrast, a third mouse model of hypertrophic cardiomyopathy due to activated NFAT3 cardiac-specific expression was not affected by cyclosporin A. These results suggest that calcineurin may function in the long-term maintenance of cardiac hypertrophy or myopathic disease states.
J Mol Cell Cardiol 2000 Apr
PMID:Reversal of cardiac hypertrophy in transgenic disease models by calcineurin inhibition. 1075 24

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.
J Mol Med (Berl) 2000
PMID:Beta1-adrenoceptor gene variations: a role in idiopathic dilated cardiomyopathy? 1079 44

The apoptotic death of cardiomyocytes due to ischemia/reperfusion is one of the major complications of heart disease. Ischemia/reperfusion has been shown to lead to the activation of the stress-activated protein (SAP) kinases and the p38/reactivating kinase (p38/RK). In this study, the direct effect of an aqueous Flos carthami (FC) extract on SAP kinases was investigated. When isolated rat hearts were perfused by Langendorff mode with media containing FC extract prior to the induction of global ischemia and the subsequent reperfusion, SAP kinase activity was inhibited 95%. Untreated ischemic/reperfused hearts showed a 57% elevation in the activity of SAP kinase. The in vitro effect of these FC extracts on SAP kinase was also tested. At a concentration of 10 microg/ml, the aqueous FC extract resulted in 50% inhibition of SAP kinase activity in ischemic heart tissue. Our results showed that FC affected both the interaction of SAP kinase with c-jun as well as the phosphotransferase reaction. These results clearly demonstrate that extracts from Flos carthami exerted inhibitory effects on SAP kinase. The administration of the FC extract may lead to a modulation of the apoptotic effect of SAP kinase activation induced during ischemia/reperfusion.
Mol Cell Biochem 2000 Apr
PMID:Effect of Flos carthami on stress-activated protein kinase activity in the isolated reperfused rat heart. 1088 25

Hereditary hemochromatosis (HH) is common among Caucasians; reported disease frequencies vary from 0.3 to 0.8%. Identification of a candidate HFE gene in 1996 was soon followed by the description of two ancestral mutations, i.e., c.845G-->A (C282Y) and c.187C-->G (H63D). To these was recently added the mutation S65C, which may represent a simple polymorphism. The incidence of HH in Greece is unknown but clinical cases are rare. Also unknown is the carrier frequency of the two mutant alleles. A first estimate of the latter is given in the present report. It is based on data from the genetic analysis of 10 unrelated patients of Greek origin who were referred to our center for genotyping and 158 unselected male blood donors. The allele frequencies for the C282Y and H63D mutations were 0.003 and 0.145, respectively. The C282Y allele was detected in 50% of HH patients. This is considerably lower than the frequencies reported for HH patients in the U.S.A. (82%) and France (91 %) and closer to that reported in Italy (64%). Five patients did not carry any known HFE mutation; three may represent cases of juvenile hemochromatosis, given their early onset with iron overload, hypogonadism, and heart disease. We suggest that genetic heterogeneity is more prominent in Southern Europe. It is also possible that the penetrance of the responsible genes is different across the Mediterranean.
Blood Cells Mol Dis 2000 Apr
PMID:Hereditary hemochromatosis: HFE mutation analysis in Greeks reveals genetic heterogeneity. 1100 26


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