Metabolic aspects of programmed cell survival and cell death in the heart.
Normal cardiac function requires a tight interaction between metabolism, contractile function and gene expression. The main perturbation challenging this equilibrium in vivo is ischemia, which alters energy flux through the control of key enzymes. The review highlights metabolic imprints and energetic aspects of programmed cell survival, programmed cell death, and of necrosis. When sustained and severe, ischemia leads to a total collapse of energy transfer, to the accumulation of metabolic endproducts, and to the development of myocardial necrosis. When moderate, ischemia results in a coordinated cellular response including enhanced anaerobic glucose metabolism, a modification of cardiac gene expression, and the development of specific mechanisms for programmed cell survival (preconditioning, stunning, hibernation). Repetitive stress results in a decrease of contractile function, a downregulation of gene expression and an impairment of energy transfer, which eventually cause the heart to fail. When the failing heart becomes energy-depleted, the programs of cell survival are no longer operational and programmed cell death ensues. To define the point of departure from programmed cell survival to cell death remains a major challenge.
Depre
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Division of Cardiology, University of Texas Houston Medical School, Houston, USA.
Taegtmeyer
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H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival; D004734:Energy Metabolism; D015870:Gene Expression / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism
D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D006003:Glycogen; D005947:Glucose