Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our previous study demonstrated that norepinephrine (NE) induces endothelial apoptosis mainly through down-regulation of Bcl-2 protein and activation of the beta-adrenergic and caspase-2 pathways. However, whether reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) are involved in this signal transduction remains unknown. Endothelial cells cultured from neonatal rat heart were treated with 100 microM NE. Proteins of MAPKs and Bcl-2 family were assayed by Western blotting. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated nick end-labeling assay. ROS was analyzed with flow cytometry. Caspase activity was measured using specific fluorogenic substrates. Treatment with NE increased intracellular ROS level and extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 phosphorylation. Whereas the phosphorylated form of Akt was decreased. The NE-induced apoptosis was abrogated by SP600125 (a specific inhibitor of JNK). Antioxidants such as vitamin C and N-acetyl cysteine inhibited NE-induced ROS production, JNK phosphorylation, caspase activation and apoptosis. Exogenously added superoxide dismutase or catalase markedly diminished NE-induced ROS production and cell death. In conclusions, our study is the first report documenting that NE induces apoptosis in neonatal rat endothelial cells via a ROS-dependent JNK activation pathway. Antioxidants may be useful in the prevention and management of NE-mediated endothelial apoptosis during heart failure.
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PMID:Norepinephrine induces apoptosis in neonatal rat endothelial cells via a ROS-dependent JNK activation pathway. 1704 59

Primary and secondary prevention of sudden cardiac death is not sufficiently assured by medication. The (automatic) implantable cardioverter/defibrillator ((A)ICD) is able to terminate life-threatening arrhythmias (ventricular fibrillation/flutter, ventricular tachycardia) reliably. The identification and care of risk patients is of crucial importance. Initially, only survived resuscitation for ventricular fibrillation or ventricular tachycardia was regarded as a confirmed indication. Several studies (CABG patch, MADIT, MADIT II, MUSTT, DINAMIT, CAT AMIOVIRT, DEFINITE, COMPANION, SCD-HeFT) have examined the prophylactic indication for ICD therapy in risk groups. Patients with chronic state after myocardial infarction with markedly impaired left ventricular function and/or spontaneous, non-sustained ventricular tachycardia have been documented to benefit. Patients with moderately severe or severe heart failure also profit from ICD implantation, where appropriate in combination with cardiac resynchronization therapy in conduction disorders. There is divergent data on dilated cardiomyopathy. ICD is not indicated in patients with acute infarctions or undergoing elective bypass surgery.
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PMID:AICD treatment in 2004--state of the art. 1710 77

Pulmonary hypertension (PH) causes right ventricular (RV) hypertrophy and, according to the extent of pressure overload, eventual heart failure. We tested the hypothesis that the mechanical stress in PH-RV impairs the vasoreactivity of the RV coronary microvessels of different sizes with increased superoxide levels. Five-week-old male Sprague-Dawley rats were injected with monocrotaline (n=126) to induce PH or with saline as controls (n=114). After 3 wk, coronary arterioles (diameter = 30-100 microm) and small arteries (diameter = 100-200 microm) in the RV were visualized using intravital videomicroscopy. We evaluated ACh-induced vasodilation alone, in the presence of N(omega)-nitro-L-arginine methyl ester (L-NAME), in the presence of tetraethylammonium (TEA) or catalase with or without L-NAME, and in the presence of SOD. The degree of suppression in vasodilation by L-NAME and TEA was used as indexes of the contributions of endothelial nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), respectively. In PH rats, ACh-induced vasodilation was significantly attenuated in both arterioles and small arteries, especially in arterioles. This decreased vasodilation was largely attributable to reduced NO-mediated vasoreactivity, whereas the EDHF-mediated vasodilation was relatively robust. The suppressive effect on arteriolar vasodilation by catalase was similar to TEA in both groups. Superoxide, as measured by lucigenin chemiluminescence, was significantly elevated in the RV tissues in PH. SOD significantly ameliorated the impairment of ACh-induced vasodilation in PH. Robust EDHF function will play a protective role in preserving coronary microvascular homeostasis in the event of NO dysfunction with increased superoxide levels.
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PMID:Impaired NO-mediated vasodilation with increased superoxide but robust EDHF function in right ventricular arterial microvessels of pulmonary hypertensive rats. 1722 Jan 92

It has been reported that high intramyocardial peroxisome proliferator-activated receptor alpha (PPARalpha) stimulation or overexpression altered cardiac contractile function in mouse models of cardiac hypertrophy and heart failure. Nevertheless, it has never been demonstrated that clinically relevant doses of drugs stimulating PPARalpha activity such as fenofibrate increase the risk to develop heart failure in humans. To determine if fenofibrate accelerates the development of heart failure in large mammals, we have tested its effects on the progression of left ventricular dysfunction in pacing-induced heart failure in pigs. Fenofibrate treatment blunted reduction in left ventricular ejection fraction, reduced cardiac hypertrophy, and attenuated clinical signs of heart failure. Fenofibrate impeded the increase in atrial natriuretic peptide, brain natriuretic peptide, and endothelin-1 plasma levels. The expression of PPARalpha, fatty acyl-CoA-oxidase, and carnitine palmitoyltransferase-Ibeta was reduced at mRNA levels in the left ventricle from untreated heart failure pigs but maintained near normal values with fenofibrate. Fenofibrate prevented heart failure-induced overexpression of TNFalpha mRNA and enhanced catalase activity in left ventricle compared to placebo. These data suggest that a clinically relevant dose of fenofibrate does not accelerate but slows down heart failure development in the model of pacing-induced heart failure in large mammals.
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PMID:The PPARalpha activator fenofibrate slows down the progression of the left ventricular dysfunction in porcine tachycardia-induced cardiomyopathy. 1757 6

The observed 26 subjects with chronic heart failure (CHF) resulted from ischemic heart disease and it was found that the state of correlation interrelation between indices of lipid peroxidation of the antioxidant system and hemocoagulation is determined by the severity of decompensation. Patients with stage I CHF were seen to have a close direct interrelation between the content of primary and secondary by-products of lipid peroxidation and prothrombin time (PT). Patients with stage IIA CHF were observed with a close negative interrelation between the level of common lipids and recalcification time; vitamin A concentration and fibrinogen F. Patients with stage II CHF had direct interrelation between the level of common lipids, vitamins E, A and prothrombin index and inversely proportional to prothrombin time at the same time the catalase activity of the patients inversely correlated with fibrinogen F.
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PMID:[Interrelation between lipid peroxidation and indices of hemocoagulation in patients with chronic heart failure resulted from ischemic heart disease]. 1768 13

The objective of this study was to understand the mechanism of action of nitric oxide (NO) in the heart by determining whether nitric oxide (NO) released from sodium nitroprusside (SNP) induces p38 mitogen activated protein kinase (p38 MAPK) phosphorylation and whether this is mediated through a cyclic GMP (cGMP)/protein kinase G (PKG) pathway. p38 MAPK activation was examined by Western blotting of whole cell lysates of embryonic chick cardiomyocytes with antibodies specific to the native or phosphorylated forms of p38 MAPK. SNP, 1 mM, which released significant amounts of NO as determined by Griess reaction, induced p38 MAPK phosphorylation that was apparent within 10 min, was significantly (p<0.05) greater than control at 60 min and remained higher than initial levels up to the 4 h end point of the experiment. This could not be attributed to hydrogen peroxide release from SNP as catalase did not affect SNP-induced p38 MAPK phosphorylation. SB202190, a relatively selective inhibitor of p38 MAPK, mainly p38alpha MAPK, inhibited SNP-induced p38 MAPK phosphorylation. SNP-induced p38 MAPK phosphorylation was not altered by pre-treatment with the PKG inhibitor KT 5823 or by ODQ a potent and selective inhibitor of NO-sensitive guanylyl cyclase. p38 MAPK phosphorylation was not induced by the cell permeable cGMP analogue, 8-Br-cGMP. In summary, considering that new therapeutic strategies aimed at NO and p38 MAPK are being considered for myocardial injury and heart failure, these data demonstrate that SNP induces p38 MAPK phosphorylation through a pathway that is independent of NO-induced activation of cGMP/PKG pathways and suggest that non cGMP/PKG regulatory proteins leading to p38 MAPK phosphorylation merit further investigation to address this therapeutic target.
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PMID:Sodium nitroprusside activates p38 mitogen activated protein kinase through a cGMP/PKG independent mechanism. 1770 40

Extracellular matrix metalloproteinase inducer (EMMPRIN) expression is increased in myocardium from patients with dilated cardiomyopathy and animal models of heart failure. However, little is known about the regulated expression or functional role of EMMPRIN in the myocardium. In rat cardiac cells, EMMPRIN is expressed on myocytes but not endothelial cells or fibroblasts. Therefore, we tested the hypothesis that EMMPRIN expression regulates matrix metalloproteinase (MMP) activity in rat ventricular myocytes in vitro. In adult rat ventricular myocytes (ARVM), beta-adrenergic receptor (betaAR) stimulation and H(2)O(2) (24 h) each increased EMMPRIN expression as assessed by immunoblotting. Pretreatment with a catalase/superoxide dismutase mimetic or adenoviral-mediated expression of catalase or a dominant-negative c-jun N-terminal kinase-1 (JNK) mutant inhibited the betaAR- and H(2)O(2)-stimulated increases in EMMPRIN expression suggesting that EMMPRIN expression is regulated via a reactive oxygen species-dependent JNK pathway. To determine whether EMMPRIN expression regulates matrix metalloproteinase (MMP) activity, EMMPRIN activity was inhibited by adenoviral expression of an inhibitory mutant of EMMPRIN. Expression of mutant EMMPRIN inhibited the betaAR-stimulated increases in MMP2 expression and zymographic MMP activity. Thus, in cardiac myocytes betaAR stimulation induces the expression of EMMPRIN via the ROS-dependent activation of JNK. The resulting increase in EMMPRIN activity stimulates MMP expression and activity. These findings suggest that in the myocardium the regulated expression of EMMPRIN is a determinant of MMP activity and may thus play a role in myocardial remodeling.
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PMID:EMMPRIN mediates beta-adrenergic receptor-stimulated matrix metalloproteinase activity in cardiac myocytes. 1786 66

During a 3-mo period, 9 of the 15 New Zealand White rabbits used in a heart failure study developed a hemolytic anemia. The heart failure model involved the creation of an aortic insufficiency (AI) followed 2 to 6 wk later by the creation of an aortic stenosis (AS). None of the 9 animals that developed hemolytic anemia responded to medical management, and 6 of the 9 were euthanized for humane concerns. Necropsies and blood cultures were performed on all anemic animals; 7 of these cultures yielded growth of Achromobacter xylosoxidans. In addition, cultures from the heart valves of 2 rabbits yielded growth of Achromobacter xylosoxidans. We presume that the endocarditis caused by Achromobacter xylosoxidans led to the mechanical damage of red blood cells (RBCs) and subsequent intravascular hemolysis or splenic destruction of damaged RBCs, resulting in a severe, regenerative hemolytic anemia. Achromobacter xylosoxidans is an aerobic, catalase-positive, oxidase-positive, gram-negative bacillus. This organism is an environmentally resistant and opportunistic bacterium that typically inhabits aqueous environments. Microbial samples from the investigator's laboratory and equipment were collected to identify the source of the bacteria. A pressure transducer and bag of intravenous fluid were identified as sources of contamination.
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PMID:Iatrogenic hemolytic anemia and endocarditis in New Zealand white rabbits secondary to Achromobacter xylosoxidans infection. 1799 75

The present study was designed to investigate whether fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, would attenuate the acute myocardial infarction in isoproterenol-treated rat model via maintaining activities of endogenous antioxidant enzymes. Hemodynamic and electrocardiograph parameters were monitored and recorded continuously, cardiac marker enzymes and antioxidative parameters of plasma and heart tissues were measured, and histopathological examination of heart tissues was performed. Isoproterenol-treated rats showed lower of left-ventricular systolic pressure (LVSP), maximum (LVdP/dtmax) and minimum rate of developed left ventricular pressure (LVdP/dtmin), and higher of left ventricular end-diastolic pressure (LVEDP), in addition, a significant rise in ST-segment and increase in content of lactate dehydrogenase, glutamic oxalacetic transaminase, creatine kinase and malondialdehyde, as well as fall in activities of glutathione peroxidase, superoxide dismutase and catalase were observed. Oral administration of fluvastatin (5, 10 and 20 mg/kg, respectively) significantly prevented almost all the parameters of isoproterenol-induced heart failure and myocardial injury that mentioned above. The protective role of fluvastatin on isoproterenol-induced myocardial damage was further confirmed by histopathological examination. There was no significant change in heart rate in all experimental groups. Compared with control group, any indexes in sham rats treated with fluvastatin (20 mg/kg) alone were unaltered (all P>0.05). Our results suggest that fluvastatin has a significant effect on the protection of heart against isoproterenol-induced myocardial infarction through maintaining endogenous antioxidant enzyme activities.
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PMID:Cardioprotective effect of fluvastatin on isoproterenol-induced myocardial infarction in rat. 1838 69

We had reported that increased levels of endogenous ghrelin during the progression of doxorubicin-induced cardiomyopathy and heart failure might provide a compensatory self-protective effect. We investigated which pathway(s) produced these protective effects in vitro. Primary cultured cardiomyocytes were induced with doxorubicin in the presence or absence of ghrelin or a tumor necrosis factor-alpha (TNF-alpha) antagonist (etanercept). Ghrelin up-regulated TNF-alpha in a time- and dose-dependent manner. It significantly reduced cell apoptosis and markers of oxidative stress, such as malondialdehyde (MDA) content and lactate dehydrogenase (LDH) activity; it also increased anti-oxidative enzyme activity such as superoxide dismutase (MnSOD) and catalase (CAT), retained mitochondrial membrane potential and energy metabolism compared with doxorubicin alone. Moreover, ghrelin increased mitochondrial anti-apoptosis related gene protein expression such as bcl-2 and MnSOD, reduced cytoplasmic cytochrome C (Cyt C) release and strengthened the activation of NF-kappaB. All these effects were abrogated by etanercept. This suggests ghrelin affects the TNF-alpha/NF-kappaB activation pathways, up-regulating TNF-alpha, to produce anti-oxidative and anti-apoptotic effects that protected cardiomyocytes from doxorubicin-induced cytotoxicity.
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PMID:Ghrelin prevents doxorubicin-induced cardiotoxicity through TNF-alpha/NF-kappaB pathways and mitochondrial protective mechanisms. 1840 Mar 55


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