title: Cardiac energy metabolic alterations in pressure overload-induced left and right heart failure (2013 Grover Conference Series).
abstract: Pressure overload of the heart, such as seen with pulmonary hypertension and/or systemic hypertension, can result in cardiac hypertrophy and the eventual development of heart failure. The development of hypertrophy and heart failure is accompanied by numerous molecular changes in the heart, including alterations in cardiac energy metabolism. Under normal conditions, the high energy (adenosine triphosphate [ATP]) demands of the heart are primarily provided by the mitochondrial oxidation of fatty acids, carbohydrates (glucose and lactate), and ketones. In contrast, the hypertrophied failing heart is energy deficient because of its inability to produce adequate amounts of ATP. This can be attributed to a reduction in mitochondrial oxidative metabolism, with the heart becoming more reliant on glycolysis as a source of ATP production. If glycolysis is uncoupled from glucose oxidation, a decrease in cardiac efficiency can occur, which can contribute to the severity of heart failure due to pressure-overload hypertrophy. These metabolic changes are accompanied by alterations in the enzymes that are involved in the regulation of fatty acid and carbohydrate metabolism. It is now becoming clear that optimizing both energy production and the source of energy production are potential targets for pharmacological intervention aimed at improving cardiac function in the hypertrophied failing heart. In this review, we will focus on what alterations in energy metabolism occur in pressure overload induced left and right heart failure. We will also discuss potential targets and pharmacological approaches that can be used to treat heart failure occurring secondary to pulmonary hypertension and/or systemic hypertension.
authors.affiliation: Department of Pediatrics, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada.
authors.forename: Sowndramalingam
authors.initials: S
authors.lastname: Sankaralingam
authors.affiliation: Department of Pediatrics, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Lopaschuk
keywords: efficiency; energy starvation; fatty acid oxidation; glucose oxidation; glycolysis; heart failure; malonyl CoA decarboxylase; pulmonary hypertension