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

In the general population, plasma concentrations of cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptides (NT-proBNP) are useful as markers of cardiac ischemia and heart failure respectively. Whether these cardiac markers have similar diagnostic potential in chronic dialysis patients are not known. The authors studied the diagnostic value of cTnT and NT-proBNP correlated with the clinical status of 63 chronic renal failure (CRF) patients with chronic dialysis (30 males and 33 females), aged 26 to 77 years (mean +/- SD, 55.9 +/- 12.6 years). Plasma cTnT and NT-proBNP were determined by using Elecsys 2010 (Roche, Switzerland). The authors found that 23.8 per cent of the chronic dialysis patients had cTnT concentrations more than the cut-off (> or = 0.1 ng/ml) and 100 per cent of these patients had NT-proBNP concentrations over the cut-off (> 334 pg/ml). The authors could not demonstrate the statistical difference between males and females for NT-proBNP concentrations as reported in the general population. But cTnT concentrations in females were significantly less than males. The authors also found a weak correlation between the two markers, when the circulating cTnT was correlated with NT-proBNP. These results suggested that plasma cTnT in chronic dialysis patients should be a prognostic marker for cardiac ischemia by using the same cut-off as the normal population. However, plasma NT-proBNP concentrations could not be used as a heart failure marker in this group of patients and needed another cut-off value for specific use in chronic dialysis patients. Moreover, the combination of cTnT and NT-proBNP concentrations in these patients may be another choice for detection of both cardiac ischemia and heart failure in the same situation. These combination markers should improve mortality in chronic dialysis patients.
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PMID:Circulating N-terminal pro-brain natriuretic peptide and cardiac troponin T in chronic dialysis patients. 1286 69

Perinatal asphyxia is a major topic in neonatology. It has a high impact on neonatal mortality and morbidity and neurological and intellectual development of the infant. Hypoxia triggers compensatory mechanisms in the fetus and the newborn aimed to sustain adequate oxygen transport to the vital organs. Long periods of hypoxia and poor perfusion cause failure of mentioned compensative mechanisms and lead to irreversible damage in tissues. No clear-cut physiologic parameters exist which allow for an early identification of neonatal infants who are either at risk to develop brain damage or posthypoxic heart failure. In the above paper authors demonstrate new possibilities in diagnosis of perinatal asphyxia. They present cardiac troponin T, a thin filament contractile protein as a highly specific and sensitive marker of myocardial injury and hypoxia.
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PMID:[Perinatal asphyxia, known topic, new diagnostic prospects--advisability of troponin T in perinatal medicine]. 1293 57

This review discusses the role of biochemical markers of myocyte injury in patients with chronic congestive heart failure. Heart specific assays have been developed for the measurement of cardiac troponin T (cTnT), cardiac troponin I (cTnI), heart type fatty acid binding protein (H-FABP), and myosin light chain 1 (MLC-1). Concentrations of these biochemical markers increase in the absence of ischaemic events in the subset of patients with heart failure whose long term outcomes are most adverse. The markers are easy to measure serially and it is therefore easy to follow patients without inter-observer variability. The serial clinical use of these markers, separately or in combination, will sharpen our understanding of the state of heart failure.
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PMID:Biochemical markers of myocyte injury in heart failure. 1536 1

Mutations in sarcomeric proteins can lead to either hypertrophic or dilated cardiomyopathy depending on their effects on the structural and functional properties of the contractile unit of the heart. Mutations in cardiac troponin T, which binds the calcium-responsive troponin complex to alpha-tropomyosin, have been shown to result in cardiac hypertrophy or cardiac dilatation and heart failure, depending on the nature of the specific mutation. In this study, we report the identification of a novel cardiac troponin T mutation (A171S) leading to dilated cardiomyopathy and sudden cardiac death. In contrast to prior described mutations, the A171S mutation results in a significant gender difference in the severity of the observed phenotype with adult males (over 20 years of age) demonstrating more severe ventricular dilatation [left ventricular end diastolic dimension (LVEDD) 7.1 vs. 5.1cm; P=0.01, t test] and left ventricular dysfunction [left ventricular shortening fraction (LVSF) 21 vs. 34%; P=0.04, t test] than adult females. The described mutation substitutes a hydrophilic amino acid for a hydrophobic one in a highly conserved domain involved in the interaction between troponin T and alpha-tropomyosin. Interestingly, four previously described mutations within 12 amino acids of A171 lead to a hypertrophic phenotype, suggesting that further characterization of the functional consequences of the A171S mutation may lead to a better understanding of the pathophysiology of DCM and of the functional differences between HCM- and DCM-causing mutations in cardiac troponin T.
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PMID:Novel troponin T mutation in familial dilated cardiomyopathy with gender-dependant severity. 1546 34

Mutations in the cardiac troponin I (CTnI) gene occur in approximately 5% of families with familial hypertrophic cardiomyopathy (FHC) and 20 mutations in this gene that cause FHC have now been described. The clinical manifestations of CTnI mutations that cause FHC are diverse, ranging from asymptomatic with high life expectancy to severe heart failure and sudden cardiac death. Most of these FHC mutations in CTnI result in cardiac hypertrophy unlike cardiac troponin T FHC mutations. All CTnI FHC mutations investigated in vitro affect the physiological function of CTnI, but other factors such as environmental or genetic factors (other genes that may affect the CTnI gene) are likely to be involved in influencing the severity of the phenotype produced by these mutations, since the distribution of hypertrophy among affected individuals varies within and between families. CTnI mutations mainly alter myocardial performance via changes in the Ca2+ -sensitivity of force development and in some cases alter the muscle relaxation kinetics due to haemodynamic or physical obstructions of blood flow from the left ventricle.
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PMID:Cellular and molecular aspects of familial hypertrophic cardiomyopathy caused by mutations in the cardiac troponin I gene. 1552 71

Clinical chemical reference values for older persons are sparse and mostly intermixed with those for younger persons. We had a unique opportunity to obtain blood samples from volunteers who were 75 years old and living in two districts of Vienna, Austria. Consequently, we utilized stored plasma samples to obtain reference intervals for 120 apparently healthy 75-year-old participants for pro-brain natriuretic peptide (proBNP), as well as for troponin T. The N-terminal (NT)-proBNP protein assay is currently used as a diagnostic and prognostic aid in patients with heart failure and as a prognostic marker in acute coronary syndromes. Specifically, the concentration of NT-proBNP in serum or plasma aids in the prognosis of ventricular systolic dysfunction and helps to differentiate between cardiac and non-cardiac causes. The median NT-proBNP plasma value for men and women in our cohort was calculated as 98 pg/ml, comparing favorably with reported values, in that a NT-proBNP concentration less than 100 pg/ml excludes acutely decompensated heart failure. Our calculated 97.5 percentile was slightly higher (359 pg/ml) than the 97.5 percentile in a group of 50-65-year-old persons (198 and 222 pg/ml for men and women, respectively) revealing the influence of age on this parameter. Because of its high tissue-specificity, cardiac troponin T is a cardiospecific, highly sensitive marker for myocardial damage. However, the troponin T concentrations in the plasma specimens from this cohort were all below the detection limit of 0.01 ng/ml, preventing any further data handling.
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PMID:Concentrations of N-terminal pro-brain natriuretic peptide and troponin T in plasma of 75-year-old apparently healthy persons. 1557 7

Protein kinase C (PKC)-induced phosphorylation of cardiac troponin I (cTnI) depresses the acto-myosin interaction and may be important during the progression of heart failure. Although both PKCbetaII and PKCepsilon can phosphorylate cTnI, only PKCbeta expression and activity are elevated in failing human myocardium during end-stage heart failure. Furthermore, although increased cTnI phosphorylation was observed in mice with cardiac-specific PKCbeta II overexpression, no differences were observed in cTnI phosphorylation status between wild type and cardiac-specific PKCepsilon overexpression mice. A potentially important downstream effector of PKCs is p90 ribosomal S6 kinase (p90RSK), which plays an important role in cell growth by activating several transcription factors as well as Na+/H+ exchanger. Since both Ser23 and Ser24 of cTnI are contained in putative consensus sequences of p90RSK phosphorylation sites, we hypothesized that p90RSK is downstream from PKCbeta II and can be a cTnI (Ser(23/24)) kinase. p90RSK, but not ERK1/2 activation, was increased in PKCbetaII overexpression mice but not in PKCepsilon overexpression mice. p90RSK could phosphorylate cTnI in vitro with high substrate affinity but not cardiac troponin T (cTnT). To confirm the role of p90RSK in cTnI phosphorylation in vivo, we generated adenovirus containing a dominant negative form of p90RSK (Ad-DN-p90RSK). We found that the inhibition of p90RSK prevented H2O2-mediated cTnI (Ser(23/24)) phosphorylation but not ERK1/2 and PKCalpha/betaII activation. Next, we generated cardiac-specific p90RSK transgenic mice and observed that cTnI (Ser(23/24)) phosphorylation was significantly increased. LY333,531, a specific PKCbeta inhibitor, inhibited both p90RSK and cTnI (Ser(23/24)) phosphorylation by H2O2. Taken together, our data support a new redox-sensitive mechanism regulating cTnI phosphorylation in cardiomyocytes.
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PMID:Role of p90 ribosomal S6 kinase (p90RSK) in reactive oxygen species and protein kinase C beta (PKC-beta)-mediated cardiac troponin I phosphorylation. 1584 May 86

Dilated cardiomyopathy (DCM), characterized by cardiac dilatation and contractile dysfunction, is a major cause of heart failure. Inherited DCM can result from mutations in the genes encoding cardiac troponin T, troponin C, and alpha-tropomyosin; different mutations in the same genes cause hypertrophic cardiomyopathy. To understand how certain mutations lead specifically to DCM, we have investigated their effect on contractile function by comparing wild-type and mutant recombinant proteins. Because initial studies on two troponin T mutations have generated conflicting findings, we analyzed all eight published DCM mutations in troponin T, troponin C, and alpha-tropomyosin in a range of in vitro assays. Thin filaments, reconstituted with a 1:1 ratio of mutant/wild-type proteins (the likely in vivo ratio), all showed reduced Ca(2+) sensitivity of activation in ATPase and motility assays, and except for one alpha-tropomyosin mutant showed lower maximum Ca(2+) activation. Incorporation of either of two troponin T mutants in skinned cardiac trabeculae also decreased Ca(2+) sensitivity of force generation. Structure/function considerations imply that the diverse thin filament DCM mutations affect different aspects of regulatory function yet change contractility in a consistent manner. The DCM mutations depress myofibrillar function, an effect fundamentally opposite to that of hypertrophic cardiomyopathy-causing thin filament mutations, suggesting that decreased contractility may trigger pathways that ultimately lead to the clinical phenotype.
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PMID:Dilated cardiomyopathy mutations in three thin filament regulatory proteins result in a common functional phenotype. 1592 95

Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair following myocardial injury, but this approach is limited by their poor viability after transplantation. To reduce cell loss after transplantation, we introduced the fibroblast growth factor-2 (FGF-2) gene ex vivo before transplantation. The isolated MSCs produced colonies with a fibroblast-like morphology in 2 weeks; over 95% expressed CD71, and 28% expressed the cardiomyocyte-specific transcription factor, Nkx2.5, as well as a-skeletal actin, Nkx2.5, and GATA4. In hypoxic culture, the FGF-2-transfected MSCs (FGF-2-MSCs) secreted increased levels of FGF-2 and displayed a threefold increase in viability, as well as increased expression of the anti-apoptotic gene, Bcl2, and reduced DNA laddering. They had functional adrenergic receptors, like cardiomyocytes, and exposure to norepinephrine led to phosphorylation of ERK1/2. Viable cells persisted 4 weeks after implantation of 5.0 yen 105 FGF-2-MSCs into infarcted myocardia. Expression of cardiac troponin T (CTn T) and a voltage-gated Ca2+ channel (CaV2.1) increased, and new blood vessels formed. These data suggest that genetic modification of MSCs before transplantation could be useful for treating myocardial infarction and end-stage cardiac failure.
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PMID:Transfection of mesenchymal stem cells with the FGF-2 gene improves their survival under hypoxic conditions. 1599 58

Cardiac troponin I (cTnI) and cardiac troponin T (cTnT) are valuable heart markers in patients presenting with symptoms of ischaemic heart disease. A number of categories of patients frequently have raised concentrations of cardiac troponin (cTn) without having ischaemic heart disease. These include patients with heart diseases such as heart failure, myocarditis and valvular disease but also those with lung emboli, renal failure and sepsis. Possible underlying mechanisms are diffuse necrosis, cTn proteolysis or leakage of cytoplasmatic cTn with no irreversible damage to the contraction complex of heart-muscle cells. It is possible that cTn-measurement in patients with non-cardiac conditions is of prognostic value but so far this has only been demonstrated in dialysis patients and patients with pulmonary embolism.
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PMID:[The significance of elevated troponin levels in the absence of acute cardiac ischaemia]. 1661 May 13


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