Metabolic remodeling in hypertrophied and failing myocardium: a review

The energy starvation hypothesis proposes that maladaptive metabolic remodeling antedates, initiates, and maintains adverse contractile dysfunction in heart failure (HF). Better understanding of the cardiac metabolic phenotype and metabolic signaling could help identify the role metabolic remodeling...

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Bibliographic Details
Published in:American journal of physiology. Heart and circulatory physiology 2017-09, Vol.313 (3), p.H597-H616
Main Authors: Peterzan, Mark A, Lygate, Craig A, Neubauer, Stefan, Rider, Oliver J
Format: Article
Language:English
Subjects:
Adaptation, Physiological
Animal diseases
Animal health
Animals
Cardiomegaly - metabolism
Cardiomegaly - pathology
Cardiomegaly - physiopathology
Cardiovascular disease
Disease Progression
Domains
Energy
Energy Metabolism
Flexibility
Genotype & phenotype
Heart Failure - metabolism
Heart Failure - pathology
Heart Failure - physiopathology
Humans
Metabolism
Myocardium
Myocardium - metabolism
Myocardium - pathology
Phenotype
Signal transduction
Signaling
Substrates
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Summary:The energy starvation hypothesis proposes that maladaptive metabolic remodeling antedates, initiates, and maintains adverse contractile dysfunction in heart failure (HF). Better understanding of the cardiac metabolic phenotype and metabolic signaling could help identify the role metabolic remodeling plays within HF and the conditions known to transition toward HF, including "pathological" hypertrophy. In this review, we discuss metabolic phenotype and metabolic signaling in the contexts of pathological hypertrophy and HF. We discuss the significance of alterations in energy supply (substrate utilization, oxidative capacity, and phosphotransfer) and energy sensing using observations from human and animal disease models and models of manipulated energy supply/sensing. We aim to provide ways of thinking about metabolic remodeling that center around metabolic flexibility, capacity (reserve), and efficiency rather than around particular substrate preferences or transcriptomic profiles. We show that maladaptive metabolic remodeling takes multiple forms across multiple energy-handling domains. We suggest that lack of metabolic flexibility and reserve (substrate, oxidative, and phosphotransfer) represents a final common denominator ultimately compromising efficiency and contractile reserve in stressful contexts.
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.00731.2016