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)

The reproducibility of the phosphocreatine to adenosine triphosphate ratio (PCr/ATP) was assessed from cardiac phosphorus-31 (31P) NMR spectra of the human left ventricle acquired with three different localization techniques. Cardiac 31P-NMR spectra (n = 68) were obtained at rest from 16 healthy subjects with three-dimensional (3D) image selected in vivo spectroscopy (ISIS), 1D spectroscopic imaging (SI), or with a combination of 2D ISIS and the 1D SI technique (ISIS + SI). The average PCr/ATP ratios were 1.41 +/- 0.20 for ISIS + SI and 1.31 +/- 0.19 for ISIS and were in the lower range of values obtained in previous studies, mainly because of a lower saturation correction factor for the cardiac PCr/ATP ratio. The SI experiment yielded an average PCr/ATP value of 0.98 +/- 0.20, significantly lower as compared to the correct values obtained with ISIS + SI and ISIS (p < 0.001), underscoring the need for 3D localization to avoid contamination of the NMR signal by liver tissue. Intersubject standard deviations of the PCr/ATP ratio were comparable to values reported previously. For all three localization techniques the absolute intra-examination differences in PCr/ATP (0.06 for ISIS to 0.15 for ISIS + SI) were significantly smaller (p approximately 0.03) than inter-examination differences (0.24 for ISIS to 0.29 for ISIS + SI). Therefore, consecutive acquisition of cardiac 31P-NMR spectra from the same patient during a single examination, e.g. under various cardiac loading conditions, appears to be a reliable approach for metabolic evaluation of heart disease.
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PMID:Reproducibility of human cardiac 31P-NMR spectroscopy. 906 3

Hypertrophic cardiomyopathy is a human heart disease characterized by increased ventricular mass, focal areas of fibrosis, myocyte, and myofibrillar disorganization. This genetically dominant disease can be caused by mutations in any one of several contractile proteins, including beta cardiac myosin heavy chain (beta MHC). To determine whether point mutations in human beta MHC have direct effects on interfering with filament assembly and sarcomeric structure, full-length wild-type and mutant human beta MHC cDNAs were cloned and expressed in primary cultures of neonatal rat ventricular cardiomyocytes (NRC) under conditions that promote myofibrillogenesis. A lysine to arginine change at amino acid 184 in the consensus ATP binding sequence of human beta MHC resulted in abnormal subcellular localization and disrupted both thick and thin filament structure in transfected NRC. Diffuse beta MHC K184R protein appeared to colocalize with actin throughout the myocyte, suggesting a tight interaction of these two proteins. Human beta MHC with S472V mutation assembled normally into thick filaments and did not affect sarcomeric structure. Two mutant myosins previously described as causing human hypertrophic cardiomyopathy, R249Q and R403Q, were competent to assemble into thick filaments producing myofibrils with well defined I bands, A bands, and H zones. Coexpression and detection of wild-type beta MHC and either R249Q or R403Q proteins in the same myocyte showed these proteins are equally able to assemble into the sarcomere and provided no discernible differences in subcellular localization. Thus, human beta MHC R249Q and R403Q mutant proteins were readily incorporated into NRC sarcomeres and did not disrupt myofilament formation. This study indicates that the phenotype of myofibrillar disarray seen in HCM patients which harbor either of these two mutations may not be directly due to the failure of the mutant myosin heavy chain protein to assemble and form normal sarcomeres, but may rather be a secondary effect possibly resulting from the chronic stress of decreased beta MHC function.
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PMID:Point mutations in human beta cardiac myosin heavy chain have differential effects on sarcomeric structure and assembly: an ATP binding site change disrupts both thick and thin filaments, whereas hypertrophic cardiomyopathy mutations display normal assembly. 910 42

Most reasonable cause of diabetic cardiopathy might be the impaired energy fuel supply and metabolism producing inevitably a hypotic condition and needing myocardial cytoprotection. Under diabetic conditions glucose disposal of the heart muscle-decreases, but working myocardial cell remains penetrable for glucose even in the absence of insulin. Therefore, it is worth to stimulate aerobic glycolysis to protect diabetic heart from frequent ischaemic events induced by diabetic late complications, since fatty acids oxidation wastes more oxygen than glycolysis for ATP production. Trimetazidine has an original cytoprotective mode of action reducing oxygen demand without altering heart activity. Consequently, trimetazidine protects structure and functions of the ischemic myocardial cell. On the other hand, glycation and altered turnover of proteins play also an important role in the development of diabetic cardiopathy. Consequently, not only trimetazidine but aminoguanidine could also reduce the development of alterations in diabetic cardiopathy inhibiting the glycation of proteins. Finally, calcium antagonists are also very usefull in myocardial cytoprotection of the diabetic heart, according to the altered cellular calcium regulation and a calcium overload which play the main role in the development of diabetic cardiopathy.
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PMID:[New concepts in the therapy of diabetic cardiopathies]. 925 64

The messenger RNA of the cardiac sarcoplasmic reticulum ATP-ase (SERCA-2a) increases in the left ventricle (LV) during ontogenic development but decreases in hypertrophy induced by increased afterload. Because of the frequency of increased left ventricular overload in congenital heart disease, the authors investigated to see if these increases were likely to interfere with the normal ontogenic program of expression of the SERCA-2a gene in the LV of sheep's foetus. A preductal coarctation of the aorta was realised by banding the transverse aorta (AoT) at 93 days' gestation in 9 foetus (CoA) matched with 9 healthy twin foetus (T). All the foetus underwent haemodynamic, anatomical, histological and molecular biological investigations 4 weeks later. The concentration of SERCA-2a mRNA in the LV was measured by hybridation of a Northern blot with a rat DNAc probe normalised with RNAr 18S. A coarctation was observed in all the CoA group and in none of the T. The ratio of LV weight/body weight was increased in 65% of CoA (p < 0.0001). The concentration of SERCA-2a mRNA in the LV was much reduced in CoA (average -28.6%) of the values observed in T (p = 0.003). Left ventricular hypertrophy of the sheep's foetus induced by pathological increases of afterload surpassed or slowed down the physiological ontogenic maturation of expression of the SERCA-2a gene in abnormalities of cardiac pump function.
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PMID:[A study of the expression of sarcoplasmic reticulum calcium ATP-ase gene in the left ventricle of the sheep's fetus submitted to chronic increased afterload in utero]. 929 54

The beneficial effects of a stable prostacyclin analogue (PGI2-A), OP 41483 against myocardial ischemic injury were experimentally and clinically evaluated. In 31P-NMR study, the preischemic treatment with PGI2-A prevented myocardial ATP depletion of rat hearts which were subjected to 20 min global ischemia. In patients with congenital heart disease, the PGI2-A of 300 ng/ml was added to the glucose-insulin-potassium cardioplegia (PGI2-group), and this group was compared to control group without PGI2-A in terms of postoperative maximal leakage of CPK-MB (maxCPK-MB). In patients under 1 yr or patients over 1 yr with aortic cross clamp time exceeded 120 min, the maxCPK-MB was significantly (p < 0.05) reduced as compared to the control. This stable PGI2 analogue has shown significant myocardial protective effects experimentally and also in clinical setting.
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PMID:[Experimental and clinical assessment of myocardial protective effect of a prostacyclin analogue (OP 41483)]. 930 17

Copper is an essential trace element and has profound influence on cardiac myopathy and heart metabolism. Dietary Cu restriction in rats results in cardiomyopathy, and affects the integrity of the basal lamina of cardiac myocytes and capillaries. Decreased levels of delta subunits of ATP synthetase and nuclear encoded subunits of cytochrome oxidase system have been observed. Alteration in expression of glutathione peroxidase and catalase in heart and liver in Cu deficiency (Cu-) has been noted involving both transcriptional and post transcriptional mechanisms. A short description of two genetically inherited disorders of Cu metabolism, i.e. Wilson's disease and Menkes' disease, and Indian childhood cirrhosis (environmental and/or genetic) have been included to illustrate that advances in the knowledge of Cu cellular transport gives a better understanding of the molecular basis of the pathophysiology of these diseases. Menkes' disease, a human model of defective Cu transport and Cu- has shown many pathological changes, similar to those of heart disease in Cu-. The recent cloning of four genes of putative Cu pumping ATPases (Cu-ATPases) from widely different sources, i.e. two from Enterococcus hirae and one each from Wilson's and Menkes disease patients (which are defective in Cu transport and metabolism), has opened a new chapter in the study of Cu cellular transport and metabolism. The encoded gene products, i.e. Cu-ATPases, show extensive homology and are members of a new class of ATP-driven Cu pumps involved in regulation of cellular Cu. Further, Cu transport by Cop B-ATPase (E. hirae) in membrane vesicles and in isolated rat liver plasma membrane has provided biochemical evidence of its role in ATP-driven Cu transport. In this short review I have critically examined the current evidence of the molecular basis of the pathophysiology of cardiomyopathy in Cu- and, have indicated the possible role of P-type Cu ATPase which may be one of the obligatory factors contributing to cardiomyopathy in experimental animals and probably humans. Experimental verification of this hypothesis will be the aim of future studies.
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PMID:Copper deficiency and heart disease: molecular basis, recent advances and current concepts. 945 22

A human pediatric cardiomyocyte cell culture model of chronic cyanosis was used to assess the effects of low oxygen tension on mitochondrial enzyme activity to address the postoperative increase in lactate and decreased ATP in the myocardium and the high incidence of low-output failure with restoration of normal oxygen tension, after technically successful corrective cardiac surgery. Chronically hypoxic cells (PO2 = 40 mmHg for 7 days) exhibited significantly reduced activities for pyruvate dehydrogenase, cytochrome-c oxidase, succinate cytochrome c reductase, succinate dehydrogenase, and citrate synthase. The activity of NADH-cytochrome c reductase was unaffected. Lactate production and the lactate-to-pyruvate ratio were significantly greater in hypoxic cardiomyocytes. Western and Northern analysis demonstrated a decrease in the levels of various mRNA and corresponding polypeptides in hypoxic cells. Thus hypoxia influences mitochondrial metabolism through acute and chronic adaptive mechanisms, reflecting allosteric (posttranscriptional) and transcriptional modulation. Transcriptional downregulation of key mitochondrial enzyme systems can explain the insufficient myocardial aerobic metabolism and low-output failure in children with cyanotic heart disease after cardiac surgery.
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PMID:Myocardial aerobic metabolism is impaired in a cell culture model of cyanotic heart disease. 981 75

A case of neonatal catecholaminergic ventricular tachycardia is reported. Episodes of fetal tachycardia were detected in a female baby and just after birth, sustained monomorphic ventricular tachycardia of complete left bundle branch block pattern and inferior axis were recorded, suggesting a right ventricular outflow origin. Routine examination did not reveal overt heart disease. Ventricular tachycardia was induced by crying or sucking, elicited by isoproterenol infusion, and was suppressed by intravenous injection of ATP or propranolol. The baby's arrhythmia was controlled with oral propranolol. The ventricular tachycardia seemed to be caused by triggered activity.
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PMID:Neonatal catecholaminergic ventricular tachycardia--a case report. 1049 91

Alterations in the capacity to maintain normal calcium homeostasis have been suggested to underlie the reduced cellular function characteristic of the aging process, and to predispose the senescent organism to a host of diverse pathologies including cancer, heart disease, and a range of muscle and neurodegenerative diseases. Therefore, critical to the eventual treatment of many age-related diseases has been the identification of both post-translational modifications and the underlying structural changes that result in an age-related decline in the function of critical calcium regulatory proteins. In brain, multiple methionines within the calcium signaling protein calmodulin (CaM) are oxidized to their corresponding methionine sulfoxides during aging, resulting in an inability to activate a range of target proteins, including the plasma membrane (PM) Ca-ATPase involved in the maintenance of the low intracellular calcium levels necessary for intracellular signaling. Likewise, changes in the transport activity of the PM-Ca-ATPase occur during aging. In muscle, the function of the SERCA2a isoform of the Ca-ATPase within the sarcoplasmic reticulum (SR) declines during aging as a result of the nitration of selected tyrosines. The age-related loss-of-function of these critical calcium regulatory proteins are consistent with observed increases in intracellular calcium levels within senescent cells. A possible regulatory role for these post-translational modifications is discussed, since they have the potential to be reversed following the restoration of normal cellular redox conditions by intracellular repair enzymes that are specific for these post-translational modifications. It is suggested that the reversible oxidation of critical calcium regulatory proteins within excitable cells by reactive oxygen species functions to enhance cellular survival under conditions of oxidative stress by reducing the energy expenditure within excitable cells. Thus, a diminished ability to efficiently generate cellular ATP may ultimately underlie the loss of calcium homeostasis and cellular function during aging.
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PMID:Protein oxidation and age-dependent alterations in calcium homeostasis. 1079 58

The adenine nucleotide translocator (ANT), the only mitochondrial carrier for ADP and ATP, combines mitochondrial energy-producing and cytosolic energy-consuming processes. The ANT function was observed to be impaired in explanted heart tissue from patients with dilated cardiomyopathy (DCM). In order to clarify whether an altered ANT isoform composition might be responsible for the restricted ANT function, we analyzed the ANT isoform expression pattern in the myocardium of patients suffering from dilated cardiomyopathy. The ANT isoform mRNA pattern was analyzed in explanted hearts from patients with dilated cardiomyopathy (n = 29), ischemic (n = 22) and valvular cardiomyopathy (n = 7) using the polymerase chain reaction technique. Myocardium from 12 subjects without heart disease was used as control. In addition, right ventricular biopsies from 47 patients with dilated cardiomyopathy who underwent cardiac catheterization were tested. A shift in the ANT isoform transcription profile was found in heart tissue from patients with dilated cardiomyopathy, but not in those from patients with ischemic or valvular cardiomyopathy. The shift was characterized by an increase in the ANT1 mRNA percentage, a decrease in ANT2 and an unchanged ANT3 proportion. Both ventricles and the septum were affected by the shift. The alteration was also found in endomyocardial specimens taken from patients with ongoing dilated cardiomyopathy. An alteration in the ANT isoform pattern was found to be specific for dilated cardiomyopathy. It is not a general phenomenon of end-stage heart failure, but occurs already before the heart is finally damaged. Therefore, an altered ANT isoform expression appears to be a feature of a dilated cardiomyopathy-specific gene program.
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PMID:The myocardial expression of the adenine nucleotide translocator isoforms is specifically altered in dilated cardiomyopathy. 1090 36


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