Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To obtain a genomic portrait of heart failure derived from end-stage dilated cardiomyopathy (DCM), we explored expression analysis using the CardioChip, a nonredundant 10,848-element human cardiovascular-based expressed sequence tag glass slide cDNA microarray constructed in-house. RNA was extracted from the left ventricular free wall of seven patients undergoing transplantation, and five nonfailing heart samples. Cy3- and Cy5-labeled (and reverse dye-labeled) cDNA probes were synthesized from individual diseased or nonfailing adult heart RNA, and hybridized to the array. More than 100 transcripts were consistently differentially expressed in DCM >1.5-fold (versus pooled nonfailing heart, P < 0.05). Atrial natriuretic peptide was found to be up-regulated in DCM (19-fold compared to nonfailing, P < 0.05), as well as numerous sarcomeric and cytoskeletal proteins (eg, cardiac troponin, tropomyosin), stress response proteins (eg, HSP 40, HSP 70), and transcription/translation regulators (eg, CCAAT box binding factor, eIF-1AY). Down-regulation was most prominently observed with cell-signaling channels and mediators, particularly those involved in Ca(2+) pathways (Ca(2+)/calmodulin-dependent kinase, inositol 1,4,5-trisphosphate receptor, SERCA). Most intriguing was the co-expression of several novel, cardiac-enriched expressed sequence tags. Quantitative real-time reverse transcriptase-polymerase chain reaction of a selection of these clones verified expression. Our study provides a preliminary molecular profile of DCM using the largest human heart-specific cDNA microarray to date.
 ...
PMID:Global gene expression profiling of end-stage dilated cardiomyopathy using a human cardiovascular-based cDNA microarray. 1205 8

Previous studies showed that aquaporin 2 (AQP2) is elevated in the kidney of the heart failure rat suggesting that an increased amount of AQP2 contributes to water retention in heart failure. We performed the present study to determine whether angiotensin II play a role in causing an increase in the expression of arginine vasopressin (AVP) V2 and AQP2 mRNA in the kidney of the cardiomyopathic hamster. The expression of AVP V2 and AQP2 mRNA in the inner medullary collecting duct (IMCD) was measured by competitive reverse transcriptase-polymerase chain reaction (RT-PCR) before and after treatment with an angiotensin-converting enzyme inhibitor, enalapril. Our results showed that the expression of AVP V2 (0.53 +/- 0.05 v 1.03 +/- 0.15 amol/microg of total RNA, P <.01) and AQP2 mRNA (0.027 +/- 0.002 v 0.036 +/- 0.002 amol/microg of total RNA, P <.05) in the IMCD of the cardiomyopathic hamster is upregulated. Treating the cardiomyopathic hamster with enalapril for 7 days negated the changes. In situ hybridization experiments confirmed the intensity of the signals for both AVP V2 and AQP2 mRNA was more intense in the IMCD of the cardiomyopathic hamster. Enalapril treatment reduced the signal intensity to a level comparable to the normal hamster. These results suggested that the increases in the expression of AVP V2 and AQP2 mRNA are mediated by angiotensin II.
 ...
PMID:Upregulation of vasopressin V2 and aquaporin 2 in the inner medullary collecting duct of cardiomyopathic hamsters is attenuated by enalapril treatment. 1214 68

Endothelin-1 (ET-1) is considered to be involved in the development and progression of heart failure. Therefore, we analysed the expression of endothelin-converting enzyme-1 (ECE-1), endothelin receptors A (ET(A)) and B (ET(B)) mRNAs by standard-calibrated, competitive reverse transcriptase-PCR using an internal-deleted in vitro-transcribed cRNA standard. ET-1 peptide levels were measured using isoform-specific rabbit antibodies against synthetic ET-1. mRNA and protein expression was determined in the right atrial myocardium of New York Heart Association class I patients and class IV patients undergoing aorto-coronary bypass surgery. ECE-1 mRNA was upregulated in failing atrial myocardium. Furthermore, ET-1 peptide levels were increased in failing atrial myocardium. Atrial ET(A) mRNA expression was not changed, while ET(B) mRNA was downregulated in the failing atrial myocardium. Our results support an upregulation of ET-1 synthesis by induction of ECE-1 in failing atrial myocardium. Pharmacological inhibition of augmented ECE-1 expression might provide a new therapeutic perspective in the treatment of heart failure.
 ...
PMID:Increased expression of endothelin-converting enzyme-1 in failing human myocardium. 1219 94

Previous studies have shown that infection with the protozoan Trypanosoma cruzi (Chagas' disease) is associated with genetic components [human leukocyte antigen (HLA) genes and T-cell receptor (TCR) genes]. We studied the TCR Vbeta repertoire of peripheral blood lymphocytes of 23 unrelated serologically positive subjects using reverse transcriptase-polymerase chain reaction (RT-PCR). The patients, previously tested for HLA genotypes, were clinically classified as asymptomatic, arrhythmic and cardiopathic patients. Statistical analysis showed the significant increment of the Vbeta7 family in chagasics with arrhythmia compared with asymptomatic and cardiopathic patients, indicating that the frequency of this family is variable in different clinical forms of the disease and possibly that these T cells might be a marker of the progression of Chagas' disease. Based on the calculation of a Delta score the order of variability in the TCR repertoire was: patients with heart failure > asymptomatic > arrhythmic patients. The major histocompatibility complex (MHC) of the individual may influence the use of particular V genes in T-cell response to foreign antigens. We found a significant increase of the Vbeta7 family in arrhythmic patients who were DRB1*01 DQB1*0501 DPB1*0401, a marker associated with susceptibility to cardiac damage in Chagas' disease. If confirmed by further studies in a larger cohort, a possible association between the TCR Vbeta repertoire and the MHC haplotype of chagasic patients could be postulated.
 ...
PMID:Analysis of the T-cell receptor beta-chain variable-region (Vbeta) repertoire in chronic human Chagas' disease. 1236 78

Transgenic mice with cardiac-specific over-expression of tumor necrosis factor-alpha (TNF1.6) progress to dilated heart failure. A significant inflammatory response precedes functional deterioration, and may contribute to cardiac damage in this model. To evaluate the underlying molecular mechanisms, we assessed the gene expression in six groups of mouse hearts defined by age, gender, and phenotype (n = 3/group) using Affymetrix microarray analysis. Phenotype was defined as compensated (in young TNF1.6) or decompensated (in older TNF1.6) via echocardiogram. Of the >1000 transcripts altered in the compensated hearts (fold change > 2, P < 0.05 vs. wild-type (WT)), 102 were identified as immune response genes, 20 of which function in antigen presentation and processing. When comparing the compensated and decompensated hearts, >50 genes were differentially regulated, including seven immunoglobulin genes. Real-time reverse transcriptase-polymerase chain reaction and cDNA microarray confirmed the Affymetrix data. Mac3+ macrophages, CD4+ T and CD45/B220+ B-cells were identified in both compensated and decompensated hearts. However, a large amount of IgG was found deposited in areas devoid of B-lymphocytes in the myocardium of decompensated TNF1.6 mice; no such accumulation was seen in the compensated or age-matched controls. Furthermore, nuclei density analyses showed a two-fold increase in the myocardium of both compensated and decompensated TNF1.6 mice (vs. WT). This study suggests that TNF-alpha over-expression activates not only the inflammatory response, but also humoral immune responses within the transgenic hearts. The autoimmune response occurs concomitantly with cardiac decompensation and may participate in triggering the transition to failure in TNF1.6 mice.
 ...
PMID:Gene expression profiling during the transition to failure in TNF-alpha over-expressing mice demonstrates the development of autoimmune myocarditis. 1508 11

Cardiovascular diseases are associated with multiple changes in gene expression. In general, cardiac tissue is not accessible to expression analysis. This study was designed to investigate expression of cardiac significant genes in white blood cells of heart failure patients and to identify differentially expressed genes. The quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) method was used for quantification of messenger RNA (mRNA) transcripts in blood samples of 20 patients (NYHA III-IV) with severe heart failure and of 20 healthy controls (NYHA I). Total RNA was extracted from leukocytes, reverse transcribed into cDNA, amplified and quantitated by SYBR Green detection. Relative mRNA expression was calculated using phosphoglycerate kinase-1 ( PGK-1) gene expression as an endogenous reference. Identified were 14 genes relevant to cardiomyocyte excitability or contractility. Most of them had not been previously reported to be expressed in blood cells. Data was based on 0.5 micro g total RNA applied to RT-PCR and on leukocyte number. In both, an increased transcription level of the Na/Ca exchanger ( NCX) was found in blood of heart failure patients as compared to controls (p < 0.02), in line with an upregulated NCX expression known from myocardial tissue of heart failure patients. This pilot study demonstrates that NCX transcription increased in potential relation to heart failure disease.
 ...
PMID:Real-time RT-PCR for gene expression profiling in blood of heart failure patients-a pilot study: gene expression in blood of heart failure patients. 1508 8

Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) secretion is rarely observed in breast carcinoma and only four cases have been previously published. We report here the case of a 50-year-old woman who presented with a history of diffuse bone pain associated with multiple hepatic, pulmonary, and bone metastases. A core needle biopsy specimen revealed an invasive ductal carcinoma in the right breast. The patient subsequently developed an ACTH-dependent paraneoplastic Cushing's syndrome and she died of arrhythmia and heart failure, despite treatment. At autopsy, immunohistochemical staining showed chromogranin A and ACTH positivity in the breast tumor and a lung metastasis. The mRNA expression of the pro-opiomelanocortin (POMC) gene was detected in tumoral cells by reverse transcriptase polymerase chain reaction (RT-PCR). This is the first case of Cushing's syndrome secondary to ectopic ACTH secretion where the presence of ACTH by immunohistochemistry and the expression of the POMC gene by RT-PCR have both been demonstrated in a breast carcinoma with metastases. The clinical history and the pathologic findings are presented with the methods and results of the molecular analysis. This case illustrates an example of ectopic ACTH syndrome in a breast carcinoma with neuroendocrine (NE) differentiation. This NE phenotype is directly related to the synthesis of ACTH by the tumoral cells. It should be kept in mind that an ectopic ACTH syndrome may be produced not only by small cell carcinoma or endocrine tumors but also by breast cancer. No relationship has been established between NE features and prognostic factors or patient outcome for this peculiar type of breast carcinoma. The demonstration of mRNA POMC in breast carcinoma with NE features suggests a depression and/or an activation of the POMC gene linked to the NE differentiation.
 ...
PMID:Pro-opiomelanocortin expression in a metastatic breast carcinoma with ectopic ACTH secretion. 1523 95

Gene therapy is emerging as a realistic addition to the therapeutic arsenal in heart failure, but the search for suitable vectors for cardiac transfection is still ongoing. In this study, we explore the applicability of recombinant Semliki Forest virus (SFV) in heart failure. SFV was intracoronarily delivered 2 weeks after induction of myocardial infarction in the rat model for heart failure. Duration of SFV expression was determined, and tissue distribution was studied by histochemical, biochemical, and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses. Expression of SFV-mediated transfection in the heart reached its maximum after 48-72 h and subsided within a week. Intracoronary administration of SFV efficiently transfected the non-infarcted cardiac wall, resulting in high levels of beta-galactosidase (beta-gal) activity (1337 +/- 537 IU/mg) and lacZ RNA in the hearts of all rats, whereas brain, kidney, liver, lung, spleen, and testis were lacZ negative. In conclusion, intracoronarily delivered SFV has a favourable distribution pattern, showing expression of the transgene restricted to the heart.
 ...
PMID:Semliki Forest virus is an efficient and selective vector for gene delivery in infarcted rat heart. 1524 44

Interleukin (IL)-18 is the interferon-gamma-inducing factor and has potent proinflammatory activities. IL-18 has been recently implicated in atherosclerotic plaque instability and myocardial ischemia-reperfusion injury. However, it is unknown whether IL-18 expression is increased in human myocardium or if it has any role in heart failure. We analyzed the expression of IL-18, its receptor IL-18Ralpha, and its endogenous inhibitor, IL-18 binding protein (IL-18BP) in myocardial tissue from patients with end-stage heart failure (ischemic or dilated cardiomyopathy) and controls by use of quantitative real-time reverse transcriptase polymerase chain reaction, Western blot or immunohistochemical techniques. Plasma levels of IL-18 were also determined in 48 patients with heart failure. IL-18 mRNA and protein levels were up-regulated in the myocardium of patients with ischemic cardiomyopathy. Both ischemic and dilated myocardium showed increased IL-18Ralpha levels, suggesting potential biological effects. In addition, mRNA levels of IL-18 BP were down-regulated in the failing myocardium. Finally, plasma IL-18 levels were significantly elevated in patients with heart failure and were higher in those who died at follow-up than in survivors. The results suggest a potential role for the immunoinflammatory IL-18 signaling pathway in the pathophysiology of heart failure and identify novel therapeutic targets for future testing.
 ...
PMID:Evidence for altered interleukin 18 (IL)-18 pathway in human heart failure. 1537 32

Fetal cardiomyocytes have been proposed as a potential source of cell-based therapy for heart failure. This study examined cellular senescence in cultured human fetal ventricular cardiomyocytes (HFCs). HFCs were isolated and identified by immunocytochemistry and RT-PCR. Cells were found to senesce after 20-25 population doublings, as determined by growth arrest, morphological changes and senescence-associated beta-galactosidase activity. Using the telomeric repeat amplification protocol assay, telomerase activity was undetectable in primary HFCs. Cells were transduced to express the human reverse transcriptase subunit (hTERT) of telomerase. This resulted in greatly increased telomerase activity, but no significant lifespan extension. Analysis of telomere length in primary HFCs revealed that the senescent phenotype was not accompanied by telomere shortening. Telomeres in hTERT-positive cells were elongated in comparison with primary cells, and elongation was retained in senescent cells. Levels of the tumor suppressor protein p16INK4A increased in all senescent cells whether telomerase-positive or -negative. Senescence was accompanied by a decline in transcript levels of the polycomb gene Bmi-1, Ets1 and Ets2 transcription factors, and Id1, Id2 and Id3 helix-loop-helix proteins, suggesting roles for these genes in maintenance of cardiomyocyte proliferative capacity. In addition to offering novel insights into the behavior of human fetal cardiomyocytes in culture, these findings have implications for the development of a cell-based therapy for cardiac injury using primary fetal heart tissue.
 ...
PMID:Telomere-independent cellular senescence in human fetal cardiomyocytes. 1565 10


<< Previous 1 2 3 4 5 Next >>