Bioenergetics of the failing heart.
The heart is responsible for pumping blood throughout the blood vessels to the periphery by repeated, rhythmic contractions at variable intensity. As such the heart should permanently adjust energy production to energy utilization and is a high-energy consumer. For this the heart mainly depends on oxidative metabolism for adequate energy production and on efficient energy transfer systems. In heart failure, there is disequilibrium between the work the heart has to perform and the energy it is able to produce to fulfill its needs. This has led to the concept of energy starvation of the failing heart. This includes decreased oxygen and substrate supply, altered substrate utilization, decreased energy production by mitochondria and glycolysis, altered energy transfer and inefficient energy utilization. Mitochondrial biogenesis and its transcription cascade are down-regulated. Disorganization of the cytoarchitecture of the failing cardiomyocyte also participates in energy wastage. Finally, the failing of the cardiac pump, by decreasing oxygen and substrate supply, leads to a systemic energy starvation. Metabolic therapy has thus emerged as an original and promising approach in the treatment heart failure. This article is part of a Special Issue entitled: Mitochondria and Cardioprotection.
Ventura-Clapier
Renée
R
INSERM, U-769, F-92296 Châtenay-Malabry, France. renee.ventura@u-psud.fr
Garnier
Anne
A
Veksler
Vladimir
V
Joubert
Frédéric
F
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D006019:Glycolysis; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D008929:Mitochondria, Heart / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*
D005227:Fatty Acids; D000255:Adenosine Triphosphate