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)

Naxos disease is a recessively inherited stereotype association of arrhythmogenic cardiomyopathy with a cutaneous phenotype, characterized by peculiar woolly hair and palmoplantar keratoderma. The cardiomyopathy clinically manifests by adolescence and the symptomatic presentation is usually with syncope and/or sustained ventricular tachycardia of left bundle branch block configuration. We report the case of a 43-year-old man without any history of heart disease who was admitted to the hospital because of an episode of sustained ventricular tachycardia and troponin I elevation, in the absence of coronary artery disease. Diagnostic workup, including genetic assessment, revealed Naxos disease as the underlying cause. In this case, acute myocarditis seems to be the most plausible explanation for the nonischemic myocardial injury.
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PMID:Naxos disease presenting with ventricular tachycardia and troponin elevation. 1916 71

Heart muscle contraction is regulated by Ca(2+) binding to the thin filament protein troponin C. In cardiovascular disease, the myofilament response to Ca(2+) is often altered. Compounds that rectify this perturbation are of considerable interest as therapeutics. Plant flavonoids have been found to provide protection against a variety of human illnesses such as cancer, infection, and heart disease. (-)-Epigallocatechin gallate (EGCg), the prevalent flavonoid in green tea, modulates force generation in isolated guinea pig hearts (Hotta, Y., Huang, L., Muto, T., Yajima, M., Miyazeki, K., Ishikawa, N., Fukuzawa, Y., Wakida, Y., Tushima, H., Ando, H., and Nonogaki, T. (2006) Eur. J. Pharmacol. 552, 123-130) and in skinned cardiac muscle fibers (Liou, Y. M., Kuo, S. C., and Hsieh, S. R. (2008) Pflugers Arch. 456, 787-800; and Tadano, N., Yumoto, F., Tanokura, M., Ohtsuki, I., and Morimoto, S. (2005) Biophys. J. 88, 314a). In this study we describe the solution structure of the Ca(2+)-saturated C-terminal domain of troponin C in complex with EGCg. Moreover, we show that EGCg forms a ternary complex with the C-terminal domain of troponin C and the anchoring region of troponin I. The structural evidence indicates that the binding site of EGCg on the C-terminal domain of troponin C is in the hydrophobic pocket in the absence of troponin I, akin to EMD 57033. Based on chemical shift mapping, the binding of EGCg to the C-terminal domain of troponin C in the presence of troponin I may be to a new site formed by the troponin C.troponin I complex. This interaction of EGCg with the C-terminal domain of troponin C.troponin I complex has not been shown with other cardiotonic molecules and illustrates the potential mechanism by which EGCg modulates heart contraction.
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PMID:Solution structure of human cardiac troponin C in complex with the green tea polyphenol, (-)-epigallocatechin 3-gallate. 1954 63

The 76 amino acid N-terminal proB-type natriuretic peptide (NT-proBNP) is proposed for evaluating and monitoring heart pathologies characterized by myocardial wall stress. Strenuous exercise might generate transitory ischemia, myocardial stress, and diastolic left ventricular dysfunction, possibly inducing an increase of some biochemical parameter concentrations. An alert has been claimed owing to biochemical and instrumental signs of heart dysfunction in recreational athletes during marathon races. We studied the behaviour of NT-proBNP in 15 mountain marathoners before and after a race. The concentrations of the parameter were lower than that observed in controls at rest and were similar to that observed in professional soccer and rugby players. The concentrations significantly increased after the race. NT-proBNP is low at rest in professional athletes, and the increase after physical exercise is physiological. The marathoners, even when performing races in a high-altitude environment, show NT-proBNP concentrations similar to those of athletes from other sports disciplines, characterized by low levels of effort and by a mix of aerobic and anaerobic metabolism. The increase of NT-proBNP is linked to strenuous physical exercise and to heavy heart effort, testified also by an increase of troponin I. However, the role of the NT-proBNP could be important to screen recreational and professional marathoners to avoid possible heart problems and sudden cardiac death in subjects with occult heart disease. The results of the present study are relevant to the design and evaluation of training programs for improving strength and function of professional marathoners.
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PMID:NT-proBNP concentrations in mountain marathoners. 2039 54

The incidence of myocardial ischaemia is increasing in the obstetric population. This has been attributed to several factors including greater maternal age, the increasing incidence of obesity and diabetes, and the growing population of patients with grown-up congenital heart disease who now reach adulthood and become pregnant. A number of cases of myocardial ischaemia in pregnant women have been documented, during and after delivery, for which no cause has been established. We present a case of a nulliparous woman who developed cardiac chest pain, bradycardia, hypertension and a raised troponin I after vaginal delivery of twin boys at 36 weeks of gestation. Ischaemic electrocardiogram changes were noted. Detailed investigations demonstrated a normal coronary circulation. A patent foramen ovale was found on bubble echocardiography.
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PMID:Peripartum cardiac chest pain and troponin rise. 2083 26

Cardiac troponin, a heterotrimeric protein complex that regulates heart contraction, represents an attractive target for the development of drugs for treating heart disease. Cardiovascular diseases are one of the chief causes of morbidity and mortality worldwide. In France, however, the death rate from heart disease is remarkably low relative to fat consumption. This so-called "French paradox" has been attributed to the high level of consumption of wine in France, and the antioxidant trans-resveratrol is thought to be the primary basis for wine's cardioprotective nature. It has been demonstrated that trans-resveratrol increases the myofilament Ca(2+) sensitivity of guinea pig myocytes [Liew, R., Stagg, M. A., MacLeod, K. T., and Collins, P. (2005) Eur. J. Pharmacol. 519, 1-8]; however, the specific mode of its action is unknown. In this study, the structure of trans-resveratrol free and bound to the calcium-binding protein, troponin C, was determined by nuclear magnetic resonance spectroscopy. The results indicate that trans-resveratrol undergoes a minor conformational change upon binding to the hydrophobic pocket of the C-domain of troponin C. The location occupied by trans-resveratrol coincides with the binding site of troponin I, troponin C's natural binding partner. This has been seen for other troponin C-targeting inotropes and implicates the modulation of the troponin C-troponin I interaction as a possible mechanism of action for trans-resveratrol.
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PMID:Structure of trans-resveratrol in complex with the cardiac regulatory protein troponin C. 2122 34

There is a need for robust techniques for early and accurate diagnosis of acute coronary syndromes (ACSs), to avoid inappropriate discharge of patients. This study examined the use of frequency spectrum analysis of heart rate variability (HRV) and photoplethysmogram (PPG) waveform variability for the identification of high-risk ACS patients defined by an elevated cardiac troponin level. The study cohort comprised a convenience sample of adult patients presenting to the emergency department of the Prince of Wales Hospital over a 4 month period complaining of non-traumatic chest pain. Valid electrocardiogram (ECG) and earlobe PPG waveforms together with troponin I test results were obtained from 52 patients at presentation, 4 of which were troponin I positive (Trop 0+). Frequency spectrum analysis was performed on the beat-to-beat HRV and PPG waveform variability (PPGV). The Trop 0+ were found to have significantly higher normalized mid-frequency power (MF(nu)) in HRV (P = 0.017), PPG amplitude variability (P = 0.009) and the cross-spectrum of HRV and PPGV (P = 0.001), which were attributed to reflex sympathetic response to myocardial ischemia. MF(nu) of PPG amplitude had the best overall performance in detecting Trop 0+, with ROC area under the curve of 0.93. The results demonstrate the potential use of ear PPG waveform to identify high-risk heart disease patients, and further highlight the utility of frequency spectrum analysis of PPGV in critical care.
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PMID:Identification of high-risk acute coronary syndromes by spectral analysis of ear photoplethysmographic waveform variability. 2170 39

The aim of this study was to investigate the degree of myocardial injury following catheter radiofrequency (RF) ablation (RFA) or cryoablation and its clinical significance in children and patients with congenital heart disease. Cardiac troponin T (cTnT) or cardiac troponin I (cTnI), creatine kinase (CK), and its cardiac isoenzyme MB (CK-MB) were measured in 269 patients who underwent catheter ablation (216 RFA, 53 cryoablation) just before the procedure and again 6 hours after the end of the procedure. Follow-up studies included echocardiography and 12 lead electrocardiographics (ECGs). No clinical, ECG, nor ECG signs of ischemia were detected. Biomarkers were increased in 57.7-75.5 %. A linear regression analysis illustrated the ablation target site and the number of RF applications as a function of higher cTnI and cTnT levels, with the maximum increase due to ventricular ablation and higher numbers of RF applications. No significant difference in cTnT levels after RFA or cryoablation were observed for AV nodal reentrant tachycardia procedures and no significant differences were observed after nonirrigated tip or irrigated tip RFA in atrial wall or ventricular wall ablation. Elevations in both troponin T and troponin I levels were commonly observed after ablation, especially in ventricular wall ablation as well as with increasing numbers of radiofrequency applications. However, unlike in patients with acute coronary syndrome, these elevated levels had no specific significance. Reference values for each ablation target site were proposed in order to potentially detect additional subclinical injuries to the coronary arteries.
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PMID:Nonsymptomatic myocardial injury after radiofrequency and cryoablation: a study of children and patients with congenital heart disease. 2259 43

Cardiac troponins are the most sensitive and specific serum markers of myocardial cell injury, but they can also arise without apparent cardiac injury. Besides, acute cholecystitis may be associated with nonspecific ST-T wave changes in electrocardiography (ECG). The signs and symptoms of gallbladder and heart disease may overlap, which can make diagnosis difficult. We describe the case of a 75-year-old woman with clinical features suggestive of acute cholecystitis associated with transient ST segment elevation and elevated troponin I that, after extensive workup, did not seem to be attributable to myocardial ischemia or any other acute cardiac problem, but were exclusively related to cholecystitis. We show that cholecystitis with gallbladder distension can be the sole cause of pathological ECG changes and an increased troponin I level; this should be considered when evaluating patients with similar presentations.
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PMID:Electrocardiographic changes and false-positive troponin I in a patient with acute cholecystitis. 2305 51

Human heart failure has been associated with a low level of thin-filament protein phosphorylation and an increase in calcium sensitivity of contraction relative to both "control" human heart tissue and tissue from small animal models. However, diverse strategies of human tissue procurement and the reliance on tissue obtained from subjects with end-stage heart failure suggest this may be an incomplete characterization. Therefore, we evaluated cardiac left ventricular (LV) biopsy samples from patients with aortic stenosis undergoing valve replacement who presented either with LV hypertrophy and preserved systolic function (Hyp) or with LV dilation and reduced ejection fraction (Dil). In Hyp, total troponin I (TnI) phosphorylation was markedly increased and myosin light chain 2 (MLC2) phosphorylation was unchanged relative to a control group of patients with normal LV function. Conversely, in Dil, total TnI phosphorylation was significantly reduced compared with control subjects and MLC2 phosphorylation was increased. Site-specific analysis of TnI phosphorylation revealed phenotype-specific differences such that Hyp samples demonstrated significant increases in phosphorylation at serine 22/23 and Dil samples had significant decreases at serine 43. The ratio of phosphorylation at the two sites was biased toward serine 22/23 in Hyp and toward serine 43/45 in Dil. Western blot analysis showed that protein phosphatase-1 was reduced in Hyp and protein phosphatase-2 was reduced in Dil. These data suggest that posttranslational modifications of sarcomeric proteins, both singly and in combination, are stage specific. Defining these changes in progressive heart disease may provide important diagnostic and treatment information.
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PMID:Contractile protein phosphorylation predicts human heart disease phenotypes. 2356 7

Thanks to its polyphenols and phytochemicals, green tea is believed to have a number of health benefits, including protecting from heart disease, but its mechanism of action at the molecular level is still not understood. Here we explore, by means of atomistic simulations, how the most abundant of the green tea polyphenols, (-)-Epigallocatechin 3-Gallate (EGCg), interacts with the structural C terminal domain of cardiac muscle troponin C (cCTnC), a calcium binding protein that plays an important role in heart contractions. We find that EGCg favourably binds to the hydrophobic cleft of cCTnC consistently with solution NMR experiments. It also binds to cCTnC in the presence of the anchoring region of troponin I (cTnI(34-71)) at the interface between the E and H helices. This appears to affect the strength of the interaction between cCTnC and cTnI(34-71) and also counter-acts the effects of the Gly159Asp mutation, related to dilated cardiomyopathy. Our simulations support the picture that EGCg interacting with the C terminal domain of troponin C may help in regulating the calcium signalling either through competitive binding with the anchoring domain of cTnI or by affecting the interaction between cCTnC and cTnI(34-71).
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PMID:A computational exploration of the interactions of the green tea polyphenol (-)-Epigallocatechin 3-Gallate with cardiac muscle troponin C. 2392 4


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