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)

Troponin I is the inhibitory component of troponin, the thin filament regulatory complex in striated muscle. Separate genes encode cardiac-specific fast and slow skeletal-specific isoforms of this protein. We have previously described gene switching from the slow skeletal to the cardiac troponin I mRNA expression in developing rat heart. The purpose of this work was to characterize the expression of the different troponin isoforms in the human heart. Human cardiac and slow skeletal troponin I cDNA probes were obtained by screening an adult cardiac cDNA library and by Taq polymerase amplification of RNA from an infant's heart, respectively. We found that the cardiac troponin I isoform is tissue-specific in its expression in normal adult tissues. RNA blot analysis of cardiac ventricular RNA from infants with congenital heart disease and from an adult with cardiomyopathy revealed expression of human cardiac troponin I in all analyzed specimens. In addition, we found expression of slow skeletal troponin I mRNA and protein in infant hearts but no detectable mRNA expression in the adult heart. We conclude that troponin I isoforms are developmentally regulated in the human heart by a mechanism similar to that in the rat heart.
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PMID:Troponin I isoform expression in human heart. 193 63

Acute chest pain patients without ECG-signs of acute myocardial infarction (AMI) on admission need to be earlier and better diagnosed to reduce use of expensive intensive care beds and to treat more patients with acute recirculation therapy. We investigated whether total CK-activity, CK-MB mass, CK-MB2, myoglobin, cardiac troponin I (cTnI) and T (cTnT) measured in venous blood on admission and after 1 and 2 h could be used to identify or exclude acute myocardial damage (AMD) in 22 acute chest pain patients without ECG-signs of AMI admitted to hospital within 6 h after onset of pain. Increases in CK-MB mass, CK-MB2, myoglobin and cTnI identified AMD in three patients classified retrospectively as AMI. Likewise, CK-MB mass, CK-MB2, cTnI and cTnT increased with time in three of seven patients classified as having unstable angina pectoris. CK-MB2 and cTnI increased with time in two patients with tachycardia belonging to the other heart disease group. The remaining seven patients of the non-heart disease group showed no change in any of the cardiac markers. Thus, early serial measurements of selected cardiac markers appear useful in identifying or excluding AMD 3 h after admission in these acute chest pain patients.
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PMID:Serial measurements of cardiac markers to rule in or out acute myocardial damage less than 3 h after admission in acute chest pain patients without ECG-signs of acute myocardial infarction. 974 21

Serum cardiac troponin I-values were compared to conventionally obtained diagnosis in 319 consecutive patients suspected of having myocardial infarction, of which 46 patients were given this diagnosis. All patients with troponin I > 20 micrograms/l (n = 40) also had abnormal creatine kinase and abnormal creatine kinase isoenzyme MB activity. All patients with troponin I values in the range 1.0-19.9 micrograms/l (n = 50) had a diagnosis of heart disease (myocardial angina pectoris, myocardial infarction, arrythmia, heart insufficiency). In this patient group, the creatine kinase measurements showed pathological values in only 12 cases. Troponin I seems to be a sensitive indicator of cardiac cell injury, and measurements of troponin I seems to be useful in ruling out cardiac injury.
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PMID:[Measurement of troponin I levels in suspected myocardial infarction]. 1059 46

The diagnosis of myocardial infarction (MI) is established in patients with chest pain and equivocal electrocardiogram changes by demonstrating a rise in blood levels of creatine kinase MB (CK-MB) and/or an increase in cardiac troponin I (cTnI) or cardiac troponin T (cTnT). Previous studies have shown that levels of CK-MB are increased in the left ventricle of individuals with heart disease; however, it has not been established whether there are differences in the ventricular myocardium concentrations of cTnI in diseased compared to healthy hearts. Using a simple extraction technique, concentrations of CK-MB and cTnI were measured in the left ventricle (LV) of six hearts obtained at autopsy from individuals ranging in age from 25 to 79 yr, with and without evidence of cardiac disease. The results show an 86-fold higher concentration of CK-MB and 7.7-fold lower concentration of cTnI in left ventricular myocardium of older men with and without cardiac disease, compared to that of younger men (< age 35 yr) without heart disease. These data suggest that age may need to be considered when setting cutoff limits for these markers for the diagnosis of myocardial infarction.
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PMID:Differences of creatine kinase MB and cardiac troponin I concentrations in normal and diseased human myocardium. 1184 17

OBJECTIVE: To investigate the correlation between RFCA catheter cumulative energy and autonomic nerve injury. METHODS: Forty-one patients with paroxysmal supraventricular tachycardia were enrolled, Patients were excluded if they had Diabetes, Hypertension, Congestive Heart Failure or other organic heart disease. HRV and biochemical markers were measured before and after the RFCA. RESULTS: Compared with pre-ablation values,there was significantly decrease in post-ablation low frequency (LF) and high frequency (HF). This was noted in both the septal group (AVNRT and septal pathway) and free wall group (free wall accessory pathway).Post-procedure,the sensitivity of cardiac troponin I(cTnI) for myocardial injury detection was 58.3%, AST was 41.7%. This was significantly higher than other markers(CK:4.2%, CK-MB:10.4%, LDH:20.8%). The post-ablation sensitivity of cTnI was 54.2%, 6.3% and 52.1%at 1 hour, 12 hours, and 24 hours respectively. A significant correlation between cumulative energy and delta HF(r=0.688,P=0.01) or delta LF (r=0.462, P<0.05).was noted in free wall group.(delta HF=pre-ablation HF-post-ablation HF/pre-ablation HF x 100%). There was no significant correlation between biochemical markers and either delta HF or delta LF. CONCLUSION: RFCA induced injury on cardiac autonomic nerves related to both cumulative energy and ablation site,but not size of myocardial injury as determined by cTnI measurement. cTnI is an excellent biochemical marker of myocardial injury.
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PMID:[Radiofrequency catheter ablation autonomic nerve injury] 1259 13

Heart disease is the leading cause of mortality and morbidity in the world. As such, biomarkers are needed for the diagnosis, prognosis, therapeutic monitoring and risk stratification of acute injury (acute myocardial infarction (AMI)) and chronic disease (heart failure). The procedure for biomarker development involves the discovery, validation, and translation into clinical practice of a panel of candidate proteins to monitor risk of heart disease. Two types of biomarkers are possible; heart-specific and cardiovascular pulmonary system monitoring markers. Here we review the use of MS in the process of cardiac biomarker discovery and validation by proteomic analysis of cardiac myocytes/tissue or serum/plasma. An example of the use of MS in biomarker discovery is given in which the albumin binding protein sub-proteome was examined using MALDI-TOF MS/MS. Additionally, an example of MS in protein validation is given using affinity surface enhanced laser desorption ionization (SELDI) to monitor the disease-induced post-translational modification and the ternary status of myocyte-originating protein, cardiac troponin I in serum.
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PMID:Heart disease, clinical proteomics and mass spectrometry. 1550 50

Transgenic and knockout mice can be used to study the genes and basic mechanisms involved in heart disease, and have therefore assumed a central role in modern cardiac research. MRI and MRS techniques have recently been developed for mice that enable the quantitative or semi-quantitative in vivo assessment of cardiac anatomy, function, perfusion, infarction, Ca(2+) influx, and metabolism. With these techniques, the normal mouse heart has been shown to be well suited as a model of human cardiac disease. The roles of individual genes in normal cardiac physiology have recently been studied by MR, including the role of neuronal nitric oxide synthase in beta-adrenergic stimulation, the roles of the inducible nitric oxide synthase and myoglobin in function, dilation, and energetics, and the role of cardiac troponin I in contractility. Furthermore, with a mouse model of myocardial infarction, the roles of the angiotensin II type 2 receptor, xanthine oxidase inhibitors, blood coagulation factor XIII, and inducible nitric oxide synthase in post-infarct function and remodeling have been further elucidated. Non-invasive in vivo MRI and MRS in mice provide a unique and powerful means for phenotyping genetically engineered mice and can improve our understanding of the roles of specific genes and proteins in cardiac physiology and pathophysiology.
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PMID:MR in mouse models of cardiac disease. 1745 Nov 82

Cardiac troponin-I (cTnI) is a sensitive and specific circulating marker of cardiac injury. The amind acid sequence of canine troponin-I suggests that immunoassays designed for humans may be able to quantify canine cTnI. We sought to validate the AccuTnItrade mark system for use in the canine species. Samples of purified canine free cTnI, cardiac troponin I-C (cTnI-C), and cardiac troponin I-T-C (cTnI-T-C) were used to assess the performance characteristics of the assay. Intra-assay precision was 4.2 +/- 3.0% and inter-assay precision was 4.5 +/- 2.7%. The assay demonstrated linearity of serial dilutions from 0.015 to 30 ng/ml for all forms of cTnI (R, 0.998 to 0.999). Mean recovery of cTnI was 92.5 +/- 10.5%, of cTnI-C was 147.2 +/- 19.8%, and of cTnI-T-C was 97.3 +/- 23.5%. Specificity of the assay for the cardiac form of troponin-I was confirmed using samples spiked with canine skeletal muscle troponin-I. The AccuTnItrade mark assay was evaluated in 27 canine patients. Dogs with heart disease (cardiomyopathy or severe mitral valve disease, n = 13) had a higher mean cTnI concentration than controls (disease cTnI = 0.68 ng/ml, range 0.03-5.47 ng/ml vs. control cTnI = 0.03 ng/ml, range 0.01-0.08 ng/ml; P = 0.0003). The AccuTnItrade mark assay possesses sufficient test performance for use with canine plasma and can distinguish a cohort of dogs with heart disease from a cohort of healthy controls. The results of this study suggest that further investigations into the clinical use of the AccuTnItrade mark assay for the diagnosis of canine heart disease are warranted.
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PMID:Validation of an immunoassay for measurement of canine cardiac troponin-I. 1908 6

Duchenne muscular dystrophy (DMD) is a fatal disease of striated muscle deterioration caused by lack of the cytoskeletal protein dystrophin. Dystrophin deficiency causes muscle membrane instability, skeletal muscle wasting, cardiomyopathy, and heart failure. Advances in palliative respiratory care have increased the incidence of heart disease in DMD patients, for which there is no cure or effective therapy. Here we have shown that chronic infusion of membrane-sealing poloxamer to severely affected dystrophic dogs reduced myocardial fibrosis, blocked increased serum cardiac troponin I (cTnI) and brain type natriuretic peptide (BNP), and fully prevented left-ventricular remodeling. Mechanistically, we observed a markedly greater primary defect of reduced cell compliance in dystrophic canine myocytes than in the mildly affected mdx mouse myocytes, and this was associated with a lack of utrophin upregulation in the dystrophic canine cardiac myocytes. Interestingly, after chronic poloxamer treatment, the poor compliance of isolated canine myocytes remained evident, but this could be restored to normal upon direct application of poloxamer. Collectively, these findings indicate that dystrophin and utrophin are critical to membrane stability-dependent cardiac myocyte mechanical compliance and that poloxamer confers a highly effective membrane-stabilizing chemical surrogate in dystrophin/utrophin deficiency. We propose that membrane sealant therapy is a potential treatment modality for DMD heart disease and possibly other disorders with membrane defect etiologies.
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PMID:Chronic administration of membrane sealant prevents severe cardiac injury and ventricular dilatation in dystrophic dogs. 2023 88

Chagas heart disease, caused by the protozoan parasite Trypanosoma cruzi, is a potentially fatal cardiomyopathy often associated with cardiac autoimmunity. T. cruzi infection induces the development of autoimmunity to a number of antigens via molecular mimicry and other mechanisms, but the genesis and pathogenic potential of this autoimmune response has not been fully elucidated. To determine whether exposure to T. cruzi antigens alone in the absence of active infection is sufficient to induce autoimmunity, we immunized A/J mice with heat-killed T. cruzi (HKTC) emulsified in complete Freund's adjuvant, and compared the resulting immune response to that induced by infection with live T. cruzi. We found that HKTC immunization is capable of inducing acute cardiac damage, as evidenced by elevated serum cardiac troponin I, and that this damage is associated with the generation of polyantigenic humoral and cell-mediated autoimmunity with similar antigen specificity to that induced by infection with T. cruzi. However, while significant and preferential production of Th1 and Th17-associated cytokines, accompanied by myocarditis, develops in T. cruzi-infected mice, HKTC-immunized mice produce lower levels of these cytokines, do not develop Th1-skewed immunity, and lack tissue inflammation. These results demonstrate that exposure to parasite antigen alone is sufficient to induce autoimmunity and cardiac damage, yet additional immune factors, including a dominant Th1/Th17 immune response, are likely required to induce cardiac inflammation.
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PMID:Heat-killed Trypanosoma cruzi induces acute cardiac damage and polyantigenic autoimmunity. 2128 41


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