doi: 10.1161/CIRCHEARTFAILURE.109.885301
Editorial |
On the Control of Metabolic Remodeling in Mitochondria of the Failing Heart
From the Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.
Correspondence to Joanne S. Ingwall, PhD, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115. E-mail jingwall@rics.bwh.harvard.edu
Received June 5, 2009; accepted June 9, 2009.
Key Words: heart failure • remodeling
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
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Introduction |
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The metabolic phenotype of the failing heart may be defined as follows.1 Metabolism remodels in the failing heart, leading to a loss in energy reserve and the inability to increase ATP supply. Ultimately, this metabolic rigidity leads to a fall in ATP. The likely time line is decreased energy reserve via the phosphotransferase reactions (creatine kinase [CK] and adenylate kinase) leading to increases in ADP and AMP, triggering an increase in glycolysis. Although the contribution of glycolysis to overall ATP synthesis increases at least in the hypertrophied heart, glycolytic reserve is limited. Importantly, as heart failure evolves, ATP synthesis from oxidation of both endogenous and exogenous fatty acids by mitochondria, the major source of ATP in the heart, falls.2
Article see p 342
Remodeling of the failing myocardium is controlled by energy sensors such as AMP that lead to changes in phosphorylation state (as well as other chemical modifications) of many proteins for short-term preservation of ATP and by activation of transcription factors that coordinately control long-term remodeling of entire ATP synthesis and utilizing pathways.
Given that the requirement for ATP for all metabolic processes and for cell viability is absolute, a renewed interest in metabolism has led to identification of the molecular links between physiological and metabolic stimuli and the regulation of gene expression in the heart. We not only have identified the metabolic targets of specific nuclear receptors and DNA-binding transcriptional activators but also are beginning to learn how their signals are amplified and sustained to remodel metabolism.
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Circ Heart Fail 2009 2: 342-350.