Apoptosis in cardiac diseases--new opportunities for novel therapeutics for heart diseases.
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.
Feuerstein
G Z
GZ
DuPont Pharmaceuticals Company, Experimental Station, Wilmington, DE 19880-0400, USA.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000502:physiology; D016207:Cytokines / Q000009:adverse effects*; D002149:Energy Intake; D006133:Growth Substances / Q000502:physiology*; D006331:Heart Diseases / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D011494:Protein Kinases / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D016207:Cytokines; D006133:Growth Substances; D017382:Reactive Oxygen Species; D011494:Protein Kinases; D020169:Caspases