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)

Abnormal long-chain fatty acid metabolism has been suggested as having a role in the genesis of certain cardiac diseases, and depressed myocardial long-chain fatty acid uptake has been clinically demonstrated in some patients with hypertrophic cardiomyopathy. However, the site where long-chain fatty acid metabolism is affected in cardiomyopathy remains unclear. Although cardiac hypertrophy is reported to be induced in rats by a fat-free diet, little is known of the consequences of depressed myocardial long-chain fatty acid uptake. Sulfo-N-succinimidyl derivatives of long-chain fatty acids have been shown to irreversibly inhibit long-chain fatty acid transport. To investigate the possible linkage of abnormal long-chain fatty acid uptake with cardiac hypertrophy, myocardial long-chain fatty acid uptake was blocked in rats using a sulfo-N-succinimidyl derivative of palmitate (SSP). SSP was intraperitoneally administered to rats for 12 weeks, and its effects on physiological parameters, and cardiac morphology were studied, SSP treatment (20 mg/kg) caused a 12% increase in heart weight (663.7 +/- 33.6 mg in controls v 741.2 +/- 26.5 mg after SSP treatment) and an 11% increase in the heart weight to body weight ratio (2.46 +/- 0.10 in controls v 2.72 +/- 0.17 after SSP) without any significant change of body weight. No significant differences were observed in blood pressure, heart rate, and serum hormones (insulin and triiodothyronine) between the control and SSP-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1995 Aug
PMID:Effect of sulfo-N-succinimidyl palmitate on the rat heart: myocardial long-chain fatty acid uptake and cardiac hypertrophy. 852 23

Chronic supraventricular tachycardia (SVT) causes left ventricular (LV) dilatation and dysfunction, diminished myocyte contractile function, and abnormalities in sarcolemmal receptor systems. We hypothesized that changes in myocyte action potential characteristics and L-type Ca2+ channel (Ca2+ channel) function, which are major determinants of myocyte contractile processes, would occur with SVT cardiomyopathy. LV function and isolated myocyte contractile function were examined in 11 pigs with SVT cardiomyopathy (pace 240 bpm; 3 weeks) and 11 control pigs. With chronic SVT, LV fractional shortening fell and myocyte shortening velocity was reduced compared to controls (11 +/- 2 v 37 +/- 2%, P < 0.0001; and 32.5 +/- 1.2 v 55.7 +/- 1.6 microns/s, P < 0.0001, respectively). Isolated myocyte action potential upstroke velocity and amplitude were reduced with SVT cardiomyopathy compared to controls (92.8 +/- 4.8 v 129.5 +/- 3.1 V/s, P < 0.0001; and 98.2 +/- 2.2 v 110.3 +/- 1.3 mV, P < 0.0001, respectively). the duration of the myocyte action potential, defined as the time to 90% repolarization, was prolonged with SVT cardiomyopathy compared to controls (201.7 +/- 5.9 v 169.1 +/- 6.8 ms, P = 0.002). These specific abnormalities in the indices of myocyte contractile function and action potential characteristics which occurred with SVT cardiomyopathy were not normalized following beta-adrenergic receptor stimulation. In order to determine a potential mechanism for the changes in myocyte contractile function and action potential characteristics with SVT cardiomyopathy, Ca2+ channel function was examined in control and SVT myocytes. In SVT myocytes, peak L-type Ca2+ current (ICa) normalized to membrane capacitance and the Ca2+ channel inactivation time constant were reduced compared to controls (-2.30 +/- 0.24 v -3.79 +/- 0.28 pA/pF, P = 0.0001; and 104.0 +/- 10.8 v 199.9 +/- 27.4 ms, P = 0.005, respectively). The abnormalities in Ca2+ channel function with SVT cardiomyopathy persisted in myocytes with equivalent membrane capacitances and were not normalized with beta-adrenergic receptor stimulation. In conclusion, findings from the present study suggest that fundamental abnormalities in myocyte electrical events (action potential) and ionic flux (Ca2+ channel function) are contributory mechanisms for the depressed myocyte contractile function with SVT cardiomyopathy.
J Mol Cell Cardiol 1995 Jun
PMID:Myocyte electrophysiological properties following the development of supraventricular tachycardia-induced cardiomyopathy. 853 Dec 16

Autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVD, MIM 107970) is one of the major causes of juvenile sudden death. We have previously assigned the disease locus to chromosome 14q23-q24. Here we report on a novel variant of ARVD, which is transmitted associated to 1q42-q43 and is characterized by a concealed form, showing effort-induced polymorphic tachycardias. Since both loci ARVD1 and ARVD2 map in proximity of alpha-actinin genes, the possible implication of these myofibrillar proteins in the pathogenesis of ARVD is discussed. Two additional ARVD families, tested with markers of chromosomes 1q42-q43 and 14q23-q24, failed to show linkage, providing evidence of further genetic heterogeneity.
Hum Mol Genet 1995 Nov
PMID:A new locus for arrhythmogenic right ventricular cardiomyopathy (ARVD2) maps to chromosome 1q42-q43. 858 94

The Emery-Dreifuss Muscular Dystrophy (EDMD) is an X-linked recessive muscular disorder characterized by early contractures of the elbows, Achilles tendons and postcervical muscles, slowly progressing muscle wasting and weakness and a cardiomyopathy characterized by conduction defects. Heart block is a frequent cause of death. Finding of mutations in one of the transcripts in the critical region in distal Xq28 led to the identification of the gene responsible for the disease. We now report the sequence of the gene which is 2100 bp long and the development of a set of primers to amplify and sequence the gene from patients' DNA. Eight unrelated X-linked familial cases were studied and they all carried different mutations, showing that lack of emerin in cardiac and skeletal muscle is the cause of the X-linked disease. No mutations were found in a family where the female carrier was affected nor in a sporadic case with a well established diagnosis of EDMD. Our findings suggest genetic heterogeneity of EDMD, and that at least two genes, the X-linked STA gene and one unidentified autosomal gene, are responsible for the disease.
Hum Mol Genet 1995 Oct
PMID:Identification of new mutations in the Emery-Dreifuss muscular dystrophy gene and evidence for genetic heterogeneity of the disease. 859 7

Propolis (bee glue) is one of the major hive products of bees and is rich in flavonoids, which are known for antioxidant activities. Doxorubicin-induced myocardiopathy is the consequence of oxidative stress through the mediation of free radicals. The effect of intraperitoneal administration of propolis (50 and 100 mg/kg) was studied on cardiomyopathy produced by doxorubicin (10 mg/kg, i.v.) in rats. Serum creatine phosphokinase (CK), aspartate aminotransferase (AST), blood and tissue glutathione (GSH), and thiobarbituric acid reactive substances (TBARS) in heart were estimated to assess the status of heart muscle. An elevation of the levels of CK, AST, GSH, and TBARS was observed following doxorubicin treatment. Parallel experiments with a pretreatment of propolis significantly reduced the levels of these parameters . Biochemical observations were supplemented by histopathological examination of heart sections. The protective effect of propolis was compared with that of rutin, a known cardioprotective flavonoid. The study demonstrates the cardioprotective effect of propolis in doxorubicin-induced experimental cardiotoxicity.
Exp Mol Pathol 1995 Jun
PMID:Propolis protects against doxorubicin-induced myocardiopathy in rats. 861 23

The purpose of this study was to characterize the collagen in hereditary dilated cardiomyopathic hamster hearts, and to examine the participation of the collagen in the occurrence and progression of cardiomyopathy. BIO 53.58 hamsters (5, 10, 20 weeks old) were used as the model of dilated cardiomyopathy. Flb hamsters were used as controls. The collagen content was almost constant at any age in the Flb hamsters, but increased with age in BIO 53.58 hamsters. Type III collagen increased significantly in BIO 53.58 hamsters at 10 weeks. The acetic acid solubility of collagen decreased in BIO 53.58 hamsters as the fibrosis progressed, but was unchanged in controls. Reducible crosslinks showed a tendency to decrease progressively in BIO 53.58 hamsters. There were no differences between Flb and BIO 53.58 hamsters at 5 weeks, but its expression in BIO 53.58 hamsters at 10 and 20 weeks of age increased compared to Flb controls. These findings indicate that in the early phase of cardiomyopathy the extracellular matrix of the myocardium is rich in type III collagen. In the later phase, the matrix resembles that of hard tissues, whose collagen is mainly of type I collagen and is insoluble. These data suggest that the increased collagen synthesis may impair the cardiac function in the development of cardiomyopathy.
Mol Cell Biochem 1996 Mar 09
PMID:Alteration of extracellular matrix in dilated cardiomyopathic hamster heart. 870 81

Mitochondrial enzyme activities were examined in cardiac tissues of turkeys with spontaneous inbred cardiomyopathy. Marked declines in specific enzyme activities were noted for respiratory complexes III and V ranging from 65-90% of the control values. No significant differences in complexes I, IV and citrate synthase nor in mitochondrial DNA copy number were detected. These results suggest that specific mitochondrial enzyme defects occur in cardiac tissues during spontaneous inbred turkey cardiomyopathy.
Biochem Mol Biol Int 1996 May
PMID:Mitochondrial dysfunction in spontaneous inbred turkey cardiomyopathy. 873 29

Endothelin (ET-1) is found at elevated concentrations in the plasma of patients with heart failure and in animal models of cardiomyopathy. The peptide is a potent positive inotropic agent, the effects of which are mediated by increases in cytosolic Ca2+ in cardiomyocytes. The object of this study was to investigate at the cellular level, the actions of ET-1 on contractile function and on Ca2+ currents in heart-failed ventricular myocardium. Male New Zealand White rabbits (8 wks) were treated with twice weekly injections of epirubicin (4 mg/kg/wk, n = 7) or with saline (n = 7) for 6 wks, followed by a washout period of 2 wks. Ventricular cardiomyocytes were isolated from rabbit hearts using Langendorff perfusion with collagenase; contractile function was examined using a video microscopy method, and L-type Ca2+ currents were recorded using a whole-cell patch-clamp technique. ET-1 produced a concentration-dependent increase in contractile response (% increase from basal value) to a maximum at 1 nM ET-1 of 69 +/- 11% (mean +/- S.D.) in control cardiomyocytes and 33 +/- 6% in heart-failed cells. However, there was no significant change in the EC50 obtained with ET-1 for healthy (0.31 +/- 0.1 nM) and for failed cardiomyocytes (0.24 +/- 0.1 nM). The effects of ET-1 on L-type Ca2+ channels were similar with a peak amplitude at 1 nM ET-1 of -3.26 +/- 0.8 nA in control cardiomyocytes and -3.32 +/- 0.9 nA in heart-failed cells. The attenuation of the contractile response to ET-1 in heart-failed cells may reflect a desensitization of ET receptors as a consequence of elevated circulating levels of ET and was not reflected by alteration of transmembrane Ca2+ conductance. It is probable, therefore, that multiple signalling pathways are involved in the actions of ET on ventricular myocardium.
Mol Cell Biochem
PMID:Mechanical effects of ET-1 in cardiomyocytes isolated from normal and heart-failed rabbits. 873 41

To identify possible alterations of the L-type calcium currents (I(Ca),L) in cardiomyopathy, I(Ca),L were recorded in atrial myocytes dissociated from the nonfailing heart (NF) of patients undergoing corrective open-heart surgery and explanted failing heart (FH) of patients with dilated cardiomyopathy undergoing heart transplantation. The patch-clamp technique was applied in the single-electrode whole-cell mode. The electrophysiological properties of I(Ca),L, including cell capacitance and current density, were similar in atrial myocytes from both groups of patients. Further to identify possible alterations of the myocardial beta-adrenergic pathway in cardiomyopathy, we examined the effects of isoproterenol, forskolin, 8-Br-cAMP and IBMX on I(Ca),L in both groups of atrial myocytes. Perfusion of isoproterenol (1 microM) significantly increased the peak I(Ca),L by 515 +/- 44% in 6 atrial myocytes from NF but increased only by 135 +/- 25% in 27 atrial myocytes from FH. However, forskolin (1 microM) or 8-Br-cAMP (0.1 mM) increased the peak I(Ca),L to a similar extent in atrial myocytes from NF and FH. IBMX (20 microM) also induced a comparable increase in the peak I(Ca),L by 213 +/- 31% (n = 5) and 207 +/- 59% (n = 4) in atrial myocytes from NF and FH, respectively. The above findings suggest that in atrial myocytes obtained from FH the beta-adrenoceptor numbers might be decreased but no impairment of the signal transduction cascade occurred beyond the GTP binding proteins level.
Mol Cell Biochem
PMID:Comparison of calcium-current in isolated atrial myocytes from failing and nonfailing human hearts. 873 42

Recently, a significant activity of inducible nitric oxide synthase (iNOS) has been reported in biopsies from failing hearts due to idiopathic dilated cardiomyopathy (IDC). Thus, a potential pathophysiological role of iNOS in IDC has been stated. In order to investigate, whether iNOS expression is of pathophysiological relevance in human heart failure, we measured iNOS protein expression and cGMP content in left ventricular myocardium from non-failing and failing human hearts. Immunoblot analysis revealed iNOS protein expression in four out of six failing hearts from septic patients, whereas no iNOS-protein expression was detected in either non-failing human hearts (n = 6) or failing hearts due to IDC (n = 9), ischemic heart disease (IHD, n = 7), Becker muscular dystrophy (BMD, n = 2) and mitoxantrone-induced toxic cardiomyopathy TCM, n = 1). cGMP content was increased by 130% in septic hearts, whereas there was no cGMP increase in hearts with IDC. IHD and BMD compared to non-failing hearts. We conclude, that the induction of iNOS may play a role in contractile dysfunction observed in septic shock, but is unlikely to be of major pathophysiological importance in end-stage heart failure due to IDC, IHD, BMD and TCM.
J Mol Cell Cardiol 1996 Jan
PMID:Expression of inducible nitric oxide synthase in failing and non-failing human heart. 874 24


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