Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The three main clinical types of cardiomyopathy are: hypertrophic cardiomyopathy; dilated cardiomyopathy; and restrictive cardiomyopathy. In each case the basic cellular mechanisms still remain to be defined.
J Mol Cell Cardiol 1985 Jul
PMID:Mechanisms in cardiomyopathies. 286 88

The sequence of myocardial changes in the mouse induced by doxorubicin (Dx) treatment (10 mg/kg i.v.) has been investigated by electron microscopy with the help of the zinc iodide-osmium tetroxide (ZIO) technique. Accumulation of ZIO-reactive material, possibly oxidized glutathione and other disulfides, in the sarcoplasmic reticulum (S.R.) is among the earliest (1 h after Dx injection), more prominent and persistent findings (up to 100 days). It may have a pathogenic relationship with a number of functional and morphologic changes occurring in myocardial cells, including impairment of calcium transport and contractility, S.R. dilation up to extensive vacuolization, as well as inhibition of DNA, RNA and protein synthesis leading to atrophy and disruption of sarcomeres. The latter finding, first appearing in a few cells 4 to 7 days after Dx and progressively increasing in severity and extension during the next 3 months, may represent a key factor in the evolution of chronic cardiomyopathy to cardiac insufficiency. In most cells, only a minority of mitochondria showed obvious ultrastructural lesions, which were first observed 24 h after treatment and disappeared by the end of the first month, when no more mitochondrial damage was found outside degenerating cells. The myocardium of mice receiving multiple Dx injections (4 mg/Kg, 10 times, or 9 mg/Kg, 5 times) showed the same changes observed in animals treated with a single dose, though they were more severe and extensive.
Virchows Arch B Cell Pathol Incl Mol Pathol 1985
PMID:Early and late sarcoplasmic reticulum changes in doxorubicin cardiomyopathy. An ultrastructural investigation with the zinc iodide-osmium tetroxide (ZIO) technique. 286 24

A quantitative evaluation of structural modifications was undertaken in the myocardium of daunorubicin (DNR)-treated and razoxane (RZ)-protected mice. BDF1 mice were injected with DNR, 15 mg/kg; a second group of mice was subjected to the same conditions but, in addition, received a pretreatment of RZ, 200 mg/kg. Representative cubes of myocardial tissue were processed for viewing with the electron microscope. Five hundred myocardial cells in each group were examined for the presence of lesions which had been categorized as early, moderate, or advanced. Contrasting the total number of demonstrable lesions in each group revealed a statistically significant reduction of 38% in abnormalities present in RZ-protected mice. By category, RZ-pretreated mice showed a mitigation in the appearance of early and moderate alterations and a striking reduction in the incidence of advanced, irreversible lesions. These results indicate that the cardiomyopathy associated with DNR administration can be ameliorated by pretreatment with RZ; this protective effect is markedly exerted by preventing the development of severe, irreversible lesions in the murine myocardium; the initial, non-transient structural alteration subsequent to DNR-exposure appears to affect the myocardial sarcoplasmic reticulum.
Virchows Arch B Cell Pathol Incl Mol Pathol 1986
PMID:Mitigation of an anthracycline-induced cardiomyopathy by pretreatment with razoxane: a quantitative morphological assessment. 287 60

beta-Adrenoceptor concentrations have been measured in ventricles of rabbits with adriamycin-induced cardiomyopathy. Despite considerable cardiac hypertrophy (1.6 +/- 0.7 mean +/- S.E.M. g ventricle/kg body wt, n = 6; to 2.2 +/- 0.1) no change in beta-adrenoceptor density was observed (33.8 +/- 2.0 fmol/mg protein in membranes from cardiomyopathic rabbits compared with 36.8 +/- 3.0 for controls). Furthermore, no alteration in the profiles of high affinity agonist binding was observed, and the receptor interaction with the adenylate cyclase stimulatory coupling factor was unimpaired. These results indicate that, despite the marked changes which occur during the development of this model of low-output heart failure, the cardiac beta-adrenoceptor systems are normal.
J Mol Cell Cardiol 1988 Sep
PMID:Ventricular beta-adrenoceptors in adriamycin-induced cardiomyopathy in the rabbit. 290 8

Energy metabolism was assessed in dilated (congestive) and hypertrophic myopathic hearts from Syrian hamsters after isolated, working heart perfusion with palmitate and/or glucose as substrates. Hearts with these two types of cardiomyopathy were found to be distinctively different from control hearts, and also different from each other. Both cardiomyopathic groups had developed hypertrophy by 3 months but the dilated hearts had a decreased muscle mass by 6 months. In the hypertrophic hearts coronary flow rates per gram of non-collagen protein and, thus, oxygen delivery were markedly increased. With either substrate the hypertrophic hearts maintained more normal levels of adenosine triphosphate in contrast to the dilated hearts whose levels were approximately 50% lower than controls by 6 months of age despite similar heart rates and left ventricular systolic pressure development in all three groups. Lactate to pyruvate ratios in the diseased hearts were comparable to control values. Total coenzyme A levels were statistically lower in the dilated compared to the control group of hearts. Carnitine and its acyl esters, on the other hand, varied markedly with levels of total carnitine decreasing to 50% of control levels in both cardiomyopathic groups by 6 months. In spite of this, the mass action ratios for the carnitine acyl-CoA transferase enzyme complexes were not markedly altered in the control or myopathic hearts regardless of whether palmitate and/or glucose were the perfusate substrates. These results suggest that the decreased carnitine levels are not of sufficient magnitude at this stage in the disease to cause a decrease in cardiac function secondary to restricted energy production. Total carnitine levels were found to be increased in liver and serum of the cardiomyopathic hamsters but unchanged in skeletal muscle. Thus, the deficiency in myocardial carnitine would appear to be due to a specific myocardial problem and not due to a problem of synthesis or supply.
J Mol Cell Cardiol 1986 Mar
PMID:Energy metabolism and mechanical function in perfused hearts of Syrian hamsters with dilated or hypertrophic cardiomyopathy. 293 27

In order to identify defects in Na+-Ca2+ exchange and Ca2+-pump systems in cardiomyopathic hearts, the activities of sarcolemmal Na+-dependent Ca2+ uptake, Na+-induced Ca2+ release, ATP-dependent Ca2+ uptake and Ca2+-stimulated ATPase were examined by employing cardiomyopathic hamsters (UM-X7.1) and catecholamine-induced cardiomyopathy produced by injecting isoproterenol into rats. The rates of Na+-dependent Ca2+ uptake, ATP-dependent Ca2+ uptake and Ca2+-stimulated ATPase activities of sarcolemmal vesicles from genetically-linked cardiomyopathic as well as catecholamine-induced cardiomyopathic hearts were decreased without any changes in Na+-induced Ca2+-release. Similar results were obtained in Ca2+-paradox when isolated rat hearts were perfused for 5 min with a medium containing 1.25 mM Ca2+ following a 5 min perfusion with Ca2+-free medium. Although a 2 min reperfusion of the Ca2+-free perfused hearts depressed sarcolemmal Ca2+-pump activities without any changes in Na+-induced Ca2+-release, Na+-dependent Ca2+ uptake was increased. These results indicate that alterations in the sarcolemmal Ca2+-efflux mechanisms may play an important role in cardiomyopathies associated with the development of intracellular Ca2+ overload.
Mol Cell Biochem
PMID:Sarcolemmal Na+-Ca2+ exchange and Ca2+-pump activities in cardiomyopathies due to intracellular Ca2+-overload. 297 15

Methods for evaluating cardiac myocyte necrosis utilizing antibodies specific for the heavy or light chains of cardiac myosin are reviewed. Cell death, associated with sarcolemmal disruption, results in the leakage of myosin light chains from the cytoplasm as well as the accessibility of myosin heavy chains to exogenous specific antibodies. Measurement of plasma light chain concentration has been useful in the diagnosis of myocardial infarction, though more recently, patients with congestive cardiomyopathy associated with an inflammatory infiltrate have been identified by an elevated plasma light chain concentration. The binding of myosin heavy chains to necrotic myocytes has been useful in the study of mechanisms of ischemic cell death in cell culture, in the diagnosis and quantification of myocardial infarction, both experimentally and clinically, and more recently in the study of experimental myocarditis and cardiac transplantation. It is hoped that these methods may evolve as useful clinical tools in the identification of those cardiomyopathy patients whose course is characterized by rapid myocyte loss.
J Mol Cell Cardiol 1985 Jul
PMID:Quantifying cell death in the myocardium: myosin specific antibody in the evaluation of membrane defects. 299 33

The hamster hereditary cardiomyopathy provides a unique model for the study of membrane abnormalities during chronic congestive heart failure. It is associated with intracellular calcium accumulation, mitochondrial calcification and cell necrosis. Previous studies have shown a decrease in Na,K-ATPase activity purified from ventricle sarcolemma. The present study demonstrates a decrease in K-dependent 3-O-methylfluorescein phosphatase (3-O-MFPase) activity from 1.93 to 1.30 mumol/g wet wt. or 33% in crude homogenates from the left ventricle of 7-months-old cardiomyopathic hamsters as compared to control animals. This represents an equivalent decrease in Na, K-ATPase activity. The values are several times higher than previously published for membrane fractions of myocardium from the hamster. Concomitantly, there was an increase in intracellular Na-concentration of the myocardium of 42% whereas the K-concentration was unchanged. The decrease in Na,K-pump concentration may be of importance for the increase in intracellular sodium and ensuing calcifying necrosis observed in the myocardium of cardiomyopathic hamsters. It is emphasized that quantification of the Na,K-ATPase or Na,K-pump should preferably be performed using crude homogenates.
J Mol Cell Cardiol 1987 Jun
PMID:Heart Na,K-ATPase activity in cardiomyopathic hamsters as estimated from K-dependent 3-O-MFPase activity in crude homogenates. 304 Oct 9

Trypanosoma cruzi infection in cultured human umbilical vein endothelial cells increased basal cellular calcium levels from 55 to 110 nM, as monitored with the fluorescent probe, fura-2. It also influenced intracellular calcium such that consistently higher total levels were observed in response to bradykinin, angiotensin II and norepinephrine, as compared to similarly treated uninfected cells. However, bradykinin and angiotensin II-dependent increases in calcium, when considered as the absolute increment or fold elevation over basal, were significantly lower in infected endothelial cells. Infection also influenced changes in calcium levels due to agents that operate independently of plasma membrane receptors. In the presence of ionomycin, the magnitude and rate of rise of intracellular calcium were decreased; additionally the calcium peak was delayed and the subsequent decline slowed. Similar to the results with bradykinin and angiotensin II, infection decreased both the increment in and fold stimulation of intracellular calcium in response to ionomycin. In contrast, infection altered only the total calcium stimulated in response to oligomycin; neither the fold stimulation of, nor increment in intracellular calcium was affected. These results indicate that (1) infection by T. cruzi alters calcium homeostasis in endothelial cells under basal and stimulated conditions; (2) both receptor-dependent and receptor-independent mechanisms are affected by infection. The possible contribution of altered calcium homeostasis induced by T. cruzi in the pathogenesis of chagasic cardiomyopathy is considered.
Mol Biochem Parasitol 1988 Jun
PMID:Alterations in intracellular calcium following infection of human endothelial cells with Trypanosoma cruzi. 304 42

Cardiomyopathy of the Syrian hamster is characterized by myocardial calcium overload and focal myocardial necrosis. The cause of the myocardial calcium overload is not yet fully understood. In this study, the ultrastructural localization of calcium was determined in normal hamster hearts and in non-necrotic and necrotic myocardium of cardiomyopathic hamsters (strain BIO 82.62). In many cells from the non-necrotic myocardium of the cardiomyopathic hamsters the calcium deposits, visible as 20 nm particles, were confined to the inner leaflet of the plasma membrane, the T-tubules and the intercalated disks. This corresponds to the calcium distribution found in normal hamsters and other mammalian species. A number of morphologically normal cells, however, displayed an increased amount of calcium precipitate in the mitochondria as well as at the sarcolemma indicating that, in the cardiomyopathic hamster, focal calcium overload is detectable cytochemically in cells which otherwise do not show gross abnormalities. In cells showing morphological signs of myolytic degeneration a marked redistribution of calcium precipitate took place. Sarcolemma became devoid of calcium deposits whereas an enormous amount of clustered precipitate occurred in largely swollen mitochondria. These data are in support of a relationship between impaired ion homeostasis and degeneration events in cardiomyopathy. Furthermore, there appears to be a clear parallelism in calcium redistribution between hypoxic and cardiomyopathic myocardium.
J Mol Cell Cardiol 1988 Aug
PMID:Ultrastructural localization of calcium in the myocardium of cardiomyopathic syrian hamsters. 322 10


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