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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myosin is a chemomechanical motor that converts chemical energy into the mechanical work of muscle contraction. More than 40 missense mutations in the cardiac myosin heavy chain (MHC) gene and several mutations in the two myosin light chains cause a dominantly inherited heart disease called familial hypertrophic cardiomyopathy. Very little is known about the biochemical defects in these alleles and how the mutations lead to disease. Because removal of the light chain binding domain in the lever arm of MHC should alter myosin's force transmission but not its catalytic function, we tested the hypothesis that such a mutant MHC would act as a dominant mutation in cardiac muscle. Hearts from transgenic mice expressing this mutant myosin are asymmetrically hypertrophied, with increases in mass primarily restricted to the cardiac anterior wall. Histological examination demonstrates marked cellular hypertrophy, myocyte disorganization, small vessel coronary disease, and severe valvular pathology that included thickening and plaque formation. Skinned myocytes and multicellular preparations from transgenic hearts exhibited decreased Ca2+ sensitivity of tension and decreased relaxation rates after flash photolysis of diazo 2. These experiments demonstrate that alterations in myosin force transmission are sufficient to trigger the development of hypertrophic cardiomyopathy.
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PMID:Cardiac myosin heavy chains lacking the light chain binding domain cause hypertrophic cardiomyopathy in mice. 1036 99

A 57-year-old Japanese-Brazilian man, visiting Japan for only 9 days, was admitted to our hospital due to syncope and frequent ventricular premature beats. He grew up in a rural area of Brazil and moved to Sao Paulo in 1959 when he was 20 years old. We suspected chronic Chagas' heart disease, i.e., dilated cardiomyopathy with apical ventricular aneurysm, right bundle branch block with left anterior fascicular block, and various arrhythmias including supraventricular premature beats, ventricular premature beats and non-sustained ventricular tachycardia because he showed typical echo- and electrocardiographic features of the disease. Coronary arteriograms were normal, and left ventriculogram confirmed the existence of apical ventricular aneurysm. A left ventricle biopsy specimen showed hypertrophic cardiac muscle with mild fibrosis. The diagnosis of chronic Chagas' disease was finally confirmed by the demonstration of Trypanosoma cruzi itself in the blood as well as Trypanosoma cruzi antibodies.
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PMID:Chronic Chagas' heart disease in a Japanese-Brazilian traveler. A case report. 1050 60

In mammals, growth of the fetal heart is regulated by proliferation of cardiac muscle cells. At later stages of pre-natal life, this proliferation diminishes profoundly [1] [2] and the dramatic expansion in heart size during the transition to adulthood is due exclusively to hypertrophy of individual cardiomyocytes [3] [4] [5]. Cardiomyocyte hypertrophy also contributes to the pathology of most post-natal heart disease [6] [7] [8] [9] [10]. Within this context, numerous signal transduction pathways have been implicated as the link between the effector(s) and altered cardiac gene expression [11] [12] [13] [14] [15] [16]. A common pathway has yet to be discovered, however. Here, we found that the activity of the stress-activated kinase p38 was enhanced in both types of cardiomyocyte hypertrophy. We also found that a target of the activated p38 kinase is the cardiac transcription factor MEF2. Transgenic mice expressing a dominant-negative form of MEF2C displayed attenuated post-natal growth of the myocardium. These results provide the first evidence for a single pathway regulating both normal and pathologic cardiomyocyte hypertrophy.
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PMID:MEF2 is upregulated during cardiac hypertrophy and is required for normal post-natal growth of the myocardium. 1053 Oct 40

Cardiovascular disease is one of the leading causes of death worldwide, and has been associated with many environmental risk factors. Recent evidence has indicated the involvement of pathogens such as viruses as causative agents, and specifically identified the coxsackievirus B serogroup as the leading culprit. Not only has coxsackievirus B3 (CB3) been identified from patients with cardiovascular disease, but also infection of mice with CB3 strains can reproduce human clinical heart disease in rodents. Several mechanisms have been proposed in an attempt to distinguish between pathology mediated by direct viral destruction of cardiac muscle cells or by the virus-induced immune response directed at infected myocytes or at 'mimicked' epitopes shared between viral and cardiac antigens. To distinguish between these mechanisms, we infected a unique mouse that diminishes the extent of infection and spread of the virus, but allows complete immunity to the virus. Transgenic mice expressing interferon-gamma in their pancreatic beta cells failed to develop CB-3-induced myocarditis. This work challenges the idea of the function of the immune response and 'molecular mimicry' in the CB-3-induced autoimmune myocarditis model, and instead favors the idea of virus-mediated damage. These results emphasize the benefit of reducing the level of viremia early during infection, thereby reducing the incidence of virus-mediated heart damage and autoimmunity.
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PMID:Pancreatic expression of interferon-gamma protects mice from lethal coxsackievirus B3 infection and subsequent myocarditis. 1083 74

"Lysosomal glycogen storage disease with normal acid maltase" which was originally described by Danon et al., is characterized clinically by cardiomyopathy, myopathy and variable mental retardation. The pathological hallmark of the disease is intracytoplasmic vacuoles containing autophagic material and glycogen in skeletal and cardiac muscle cells. Sarcolemmal proteins and basal lamina are associated with the vacuolar membranes. Here we report ten unrelated patients, including one of the patients from the original case report, who have primary deficiencies of LAMP-2, a principal lysosomal membrane protein. From these results and the finding that LAMP-2-deficient mice manifest a similar vacuolar cardioskeletal myopathy, we conclude that primary LAMP-2 deficiency is the cause of Danon disease. To our knowledge this is the first example of human cardiopathy-myopathy that is caused by mutations in a lysosomal structural protein rather than an enzymatic protein.
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PMID:Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease). 1097 94

Apoptosis of cardiac muscle cells may contribute to the development of cardiomyopathy and heart failure. Alcohol (ethanol) abuse is a major cause of cardiomyopathy, but its underlying mechanism remains unknown. To determine whether ethanol causes apoptosis in cardiac muscle and whether insulin-like growth factor I (IGF 1) improves cardiac muscle survival upon ethanol exposure, we have defined the effects of ethanol and IGF I in primary cardiomyocytes. Ethanol decreased cell viability in dose-response manner from 0.2% to 1%. In contrast, ethanol (0.2-1%) did not alter viability of cardiac fibroblasts. To assess the occurrence of apoptosis, DNA fragmentation was determined with quantitation of nucleosomes. Nucleosomes were increased in ethanol-treated cells, thus confirming the apoptotic effects of ethanol. The pro-apoptotic Bax protein and Caspase 3 are important proteins of apoptotic signaling. The content of Bax and the activities of Caspase 3 were increased upon ethanol exposure. IGF I partially suppressed Bax induction, Caspase 3 activation, DNA fragmentation, and increased cardiomyocyte survival. The effects of IGF I on ethanol-induced apoptosis can be inhibited with a chemical inhibitor of PI 3 Kinase (LY-294002), suggesting that anti-apoptotic actions of IGF I involves PI 3 Kinase. These results may have important implications on further understanding the pathogenesis of alcoholic heart disease and the development of new strategies to treat alcoholic cardiomyopathy.
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PMID:Insulin-like growth factor I retards apoptotic signaling induced by ethanol in cardiomyocytes. 1102 53

There are some studies demonstrating the skeletal muscle degeneration associated with the degeneration of Z band and appearance of nemaline rods in experimental animals of the simulation model for spaceflight but not in human heart tissues. In the present study, therefore, we investigated the pathological changes or degeneration in left auricular heart muscles obtained during operations of mitral valves replacement using both electron and light microscopies. The degeneration of Z band even in the myofibrils of comparatively little damaged cell was found. Furthermore, nemaline rods were detected in most of the heart muscle cells. These results suggest that the existence of nemaline rods is involved in the cell injury in the heart muscle of patients with heart disease without nemaline myopathy. Further study is necessary to know whether the similar pathological findings are observed not only in the skeletal muscle but also in the cardiac muscle in experimental animals of the simulation model for spaceflight or in a prolonged spaceflight.
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PMID:Nemaline rod and degeneration of Z band of muscle cell in weightlessness at spaceflight. 1154 52

A 42-year-old man and a 31-year-old man with congestive heart failure caused by the thyroid stimulating hormone(TSH) secreting pituitary adenoma were reported. Heart failure was improved after transsphenoidal resection of the pituitary adenoma in each patient. The syndrome of inappropriate secretion of TSH causes hyperthyroidism. Thyroid hormone acts directly on cardiac muscle to increase the stroke volume. Hyperthyroidism itself reduces the peripheral vascular resistance and an elevated basal metabolism which is the basic physiologic change in hyperthyroidism dilates small vessels and reduces vascular resistance. The reduced vascular resistance contributes to increase stroke volume. Thyroid hormone also acts directly on the cardiac pacemakers to be apt to cause tachycardiac atrial fibrillation. These mechanical changes in hyperthyroidism increase not only the cardiac output but also the venous return. The increased blood volume and the shortened ventricular filling time due to tachycardia result in congestive heart failure. TSH secreting pituitary adenoma is a rare tumor, however heart failure is common disease. TSH secreting pituitary adenoma should be taken into consideration in patients with heart failure. The presented cases were very enlightening to understand the relation between brain tumor and heart disease.
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PMID:[Congestive heart failure caused by the thyroid stimulating hormone(TSH) secreting pituitary adenoma: report of two cases]. 1157 21

Electrical activation of the heart requires cell-cell transfer of current via gap junctions, arrays of densely packed protein channels that permit intercellular passage of ions and small molecules. Because current transfer occurs only at gap junctions, the spatial distribution and biophysical properties of gap junction channels are important determinants of the conduction properties of cardiac muscle. Gap junction channels are composed of members of a multigene family of proteins called connexins. As a general rule, individual cells express multiple connexins, which creates the potential for considerable functional diversity in gap junction channels. Although gap junction channels are relatively nonselective in their permeability to ions and small molecules, cardiac myocytes actively adjust their level of coupling by multiple mechanisms including changes in connexin expression, regulation of connexin trafficking and turnover, and modulation of channel properties. In advanced stages of heart disease, connexin expression and intercellular coupling are diminished, and gap junction channels become redistributed. These changes have been strongly implicated in the pathogenesis of lethal ventricular arrhythmias. Ongoing studies in genetically engineered mice are revealing insights into the role of individual gap junction channel proteins in normal cardiac function and arrhythmogenesis.
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PMID:The role of myocardial gap junctions in electrical conduction and arrhythmogenesis. 1160 Mar 34

As classically described, the precardiac mesoderm of the paired heart-forming fields migrate and fuse anteriomedially in the ventral midline to form the first segment of the straight heart tube. This segment ultimately forms the right trabeculated ventricle. Additional segments are added to the caudal end of the first in a sequential fashion from the posteriolateral heart-forming field mesoderm. In this study we report that the final major heart segment, which forms the cardiac outflow tract, does not follow this pattern of embryonic development. The cardiac outlet, consisting of the conus and truncus, does not derive from the paired heart-forming fields, but originates separately from a previously unrecognized source of mesoderm located anterior to the initial primitive heart tube segment. Fate-mapping results show that cells labeled in the mesoderm surrounding the aortic sac and anterior to the primitive right ventricle are incorporated into both the conus and the truncus. Conversely, if cells are labeled in the existing right ventricle no incorporation into the cardiac outlet is observed. Tissue explants microdissected from this anterior mesoderm region are capable of forming beating cardiac muscle in vitro when cocultured with explants of the primitive right ventricle. These findings establish the presence of another heart-forming field. This anterior heart-forming field (AHF) consists of mesoderm surrounding the aortic sac immediately anterior to the existing heart tube. This new concept of the heart outlet's embryonic origin provides a new basis for explaining a variety of gene-expression patterns and cardiac defects described in both transgenic animals and human congenital heart disease.
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PMID:The outflow tract of the heart is recruited from a novel heart-forming field. 1178 96


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