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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since mammalian cardiac myocytes essentially rely on aerobic energy metabolism, it has been assumed that cardiocytes die in a catastrophic breakdown of cellular homeostasis (i.e. necrosis), if oxygen supply remains below a critical limit. Recent observations, however, indicate that a process of gene-directed cellular suicide (i.e. apoptosis) is activated in terminally differentiated cardiocytes of the adult mammalian heart by ischemia and reperfusion, and by cardiac overload as well. Apoptosis or programmed cell death is an actively regulated process of cellular self destruction, which requires energy and de novo gene expression, and which is directed by an inborn genetic program. The final result of this program is the fragmentation of nuclear DNA into typical 'nucleosomal ladders', while the functional integrity of the cell membrane and of other cellular organelles is still maintained. The critical step in this regulated apoptotic DNA fragmentation is the proteolytic inactivation of poly-[ADP-ribose]-polymerase (PARP) by a group of cysteine proteases with some structural homologies to interleukin-1 beta-converting enzyme (ICE-related proteases [IRPs] such as apopain, yama and others). PARP catalyzes the ADP-ribosylation of nuclear proteins at the sites of spontaneous DNA strand breaks and thereby facilitates the repair of this DNA damage. IRP-mediated destruction of PARP, the 'supervisor of the genome', can be induced by activation of membrane receptors (e.g. FAS or APOI) and other signals, and is inhibited by activation of 'anti-death genes' (e.g. bcl-2). Overload-triggered myocyte apoptosis appears to contribute to the transition to cardiac failure, which can be prevented by therapeutic hemodynamic unloading. In myocardial ischemia, the activation of the apoptotic program in cardiocytes does not exclude their final destiny to catastrophic necrosis with release of cytosolic enzymes, but might be considered as an adaptive process in hypoperfused ventricular zones, sacrificing some jeopardized myocytes to regulated apoptosis, which may be less arrhythmogenic than necrosis with the primary disturbance of membrane function.
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PMID:Apoptosis in the heart: when and why? 897 66

Fibrosis in the heart may result from loss of myocytes, which are replaced by collagens. Apoptosis is now known to contribute to myocyte loss in the failing human heart. The mechanisms underlying the induction of cardiomyocyte apoptosis, and thus the expansion of fibrotic foci in the failing heart, are poorly understood. We hypothesized that viable heart cells adjacent to fibrotic foci might become "predisposed" to apoptosis by expression of the receptor FAS (APO1, CD95). We therefore studied the spatial relationship of FAS expression and fibrosis in patients with heart failure. Left ventricular biopsies were obtained from seven patients undergoing coronary artery bypass grafting. All patients had reduced ejection fraction but varied in New York Heart Association class score at the time of surgery. Heart cell apoptosis, fibrosis, and FAS expression were studied by propidium iodide and in situ end labeling (ISEL) of DNA, Picrosirius red staining, and immunohistochemistry. All patient samples exhibited, albeit to varying degrees, apoptosis detected by ISEL, chromatin condensation, and nuclear fragmentation. In all samples, fibrosis (collagen) was evident both perivascular and in isolated regions of scarring. Regardless of the extent of fibrosis or detectable apoptosis, FAS expression was observed in regions immediately adjacent to the fibrosis, but not in regions distal to fibrosis, nor in fibrotic areas devoid of nuclei. Expression of FAS was found adjacent to both perivascular and diffuse fibrosis, and ISEL-positive nuclei were found within cells reacting positively with anti-FAS antibodies. However, ISEL-positive nuclei were no more abundant in FAS-positive regions (67.6 +/- 5.8% of total nuclei) than in FAS-negative areas (69.5 +/- 9.8%). We conclude that expression of FAS occurs in remaining heart cells adjacent to fibrosis of either perivascular or presumed reparative origin. Although this phenomenon could contribute to the expansion of fibrotic foci, FAS-induced apoptosis in the failing heart may not be more prevalent than apoptosis initiated by other signaling mechanisms.
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PMID:Expression of FAS adjacent to fibrotic foci in the failing human heart is not associated with increased apoptosis. 1044 67

Apoptosis as defined by contemporary science describes a form of cell death that involves discrete genetic and molecular programs, de novo protein expression and unique cellular phenotype. Evidence for the existence of apoptosis in the human heart has been reported in various cardiac diseases, including ischemic and non-ischemic heart failure, myocardial infarction and arrhythmias. Among the most potent stimuli that elicit cardiomyocyte apoptosis are: oxygen radicals (including NO), cytokines, (FAS/TNF alpha family of cytokines) and growth factors/energy deprivation. Several complex signal transduction pathways have been implicated in execution of cardiomyocyte apoptosis, including: Fas/TNF alpha receptors signaling, stress or mitogen activated protein kinases (SAPK/MAPK), sphingolipids metabolites (ceramide), G-protein coupled receptor (GPCR) signaling (G alpha i, G alpha q) and NF kappa B activation. Apoptosis of cardiac myocytes may contribute to progressive pump-failure, arrhythmias and cardiac remodeling. The recognition of numerous molecular targets associated with cardiomyocyte apoptosis that are amenable for pharmacologic manipulation, may provide novel therapeutic strategies for diverse cardiac ailments, as recently suggested by pharmacologic studies in experimental animals.
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PMID:Apoptosis in cardiac diseases--new opportunities for novel therapeutics for heart diseases. 1051 63

Apoptosis is a form of cell death that involves discrete genetic and molecular programs, de novo protein expression and a unique cellular phenotype. Evidence for the existence of apoptosis in the human heart has been reported in various cardiac diseases, including ischemic and non-ischemic heart failure, myocardial infarction and arrhythmias. Among the most potent stimuli that elicit cardiomyocyte apoptosis are: oxygen radicals (including NO), cytokines (FAS/TNF alpha-receptor signaling), stress conditions (chemical or physical, e.g., radiation), sphingolipid metabolites (ceramide) and autocoids, e.g., angiotensin II. Apoptosis of cardiac myocytes may contribute to progressive pump-failure, arrhythmias and cardiac remodeling. The recognition of numerous molecular targets associated with cardiomyocyte apoptosis may provide novel therapeutic strategies for diverse cardiac ailments, as recently suggested by pharmacologic studies in experimental animals. This review paper is aimed to highlight the role of protein kinase signaling pathways in apoptosis with special attention to the stress-activated protein kinases (SAPK) and mitogen-activated protein kinases (MAPK) systems.
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PMID:Apoptosis in cardiac diseases: stress- and mitogen-activated signaling pathways. 1072 77

Apoptosis as defined by contemporary science describes a form of cell death that involves discrete genetic and molecular programs, de novo protein expression and unique cellular phenotype. Evidence for the existence of apoptosis in the human heart has been reported in various cardiac diseases, including ischemic and non-ischemic heart failure, myocardial infarction and arrhythmias. Among the most potent stimuli that elicit cardiomyocyte apoptosis are: oxygen radicals (including NO), cytokines, (e.g., TNFalpha, FAS) neurohormonal factors (angiotension II), cardiotoxic drugs (e.g., doxorubicin) and mechanical, stretch situations. Several complex signal transduction pathways have been implicated in execution of cardiomyocyte apoptosis. Most prominent are: 1) Tyrosine kinase receptors (TRK) induced signaling involving stress or mitogen activated protein kinases (SAPK/MARK) and sphingolipids metabolites (ceramide); 2) G-protein coupled receptor (GPCR) signaling (Galphai, Galphaq) and 3) NF(K) B activation. Apoptosis of cardiac myocytes may contribute to progressive pump-failure, arrhythmias and cardiac remodeling. The recognition of diverse molecular targets associated with cardiomyocyte apoptosis provide new opportunities for pharmacologic manipulation, that may lead to discovery and development of therapeutic strategies for treatment of heart failure, arrhythmias and myocardial infarction.
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PMID:Apoptosis--new opportunities for novel therapeutics for heart diseases. 1191 65

To determine the cardiovascular molecular events associated with acute exposure to cocaine, the present study utilized in vivo analysis of left-ventricular heart function in adult rabbits, fluorescence confocal microscopy of fluo-2, rhod-2, (5-(and-6) carboxy 2',7' dichlorodihydrofluores-cein diacetate (carboxy-H2DCFDA), and JC-1 in H9C2 cells and gene expression microarray technology for analysis of gene activation in both rabbit ventricular tissue and H9C2 cells. In the rabbit, acute cocaine exposure (2 mg/kg) caused left-ventricular dysfunction and 0.1-10 mM cocaine increased cytosolic and mitochondrial calcium activity and mitochondrial membrane depolarization in H9C2 cells. A 3-min pretreatment of H9C2 cells by 10 microM verapamil, nifedipine, or nadolol inhibited calcium increases, but only 1 mM N-acetylcysteine (NAC) or 1 mM glutathione blocked mitochondrial membrane depolarization. Cocaine induced activation of genes in the rabbit heart and H9C2 cells including angiotensinogen, ADRB1, and c-reactive protein (CRP). In H9C2 cells, NAC pretreatment blocked cocaine-mediated increases in CRP, FAS, FAS ligand, and cytokine receptor-like factor1 (CRLF1) expression. Collectively, these data suggest that acute cocaine administration initiates cellular and genetic changes that, if chronically manifested, could cause cardiac deficits similar to those seen in heart failure and ischemia, such as ventricular dysfunction, cardiac arrhythmias, and cardiac remodeling.
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PMID:Cocaine increases intracellular calcium and reactive oxygen species, depolarizes mitochondria, and activates genes associated with heart failure and remodeling. 1638 75