Systems biology analysis in a large animal model of HFpEF revealed early cardiac oxidative metabolism alterations at 1 month and persistent skeletal muscle mitochondrial dysfunction at 4 months.
Does aortic banding-induced pressure overload alter cardiac and skeletal muscle metabolism and transcription in a feline model of HFpEF?
Early cardiac mitochondrial dysfunction and comprehensive metabolic remodeling precede functional decline in a large animal model of HFpEF, suggesting metabolic derangements are primary drivers of the disease.
In this study the authors used systems biology to define progressive changes in metabolism and transcription in a large animal model of heart failure with preserved ejection fraction (HFpEF). Transcriptomic analysis of cardiac tissue, 1-month post-banding, revealed loss of electron transport chain components, and this was supported by changes in metabolism and mitochondrial function, altogether signifying alterations in oxidative metabolism. Established HFpEF, 4 months post-banding, resulted in changes in intermediary metabolism with normalized mitochondrial function. Mitochondrial dysfunction and energetic deficiencies were noted in skeletal muscle at early and late phases of disease, suggesting cardiac-derived signaling contributes to peripheral tissue maladaptation in HFpEF. Collectively, these results provide insights into the cellular biology underlying HFpEF progression.
Gibb et al. (Sun,) conducted a other in Heart failure with preserved ejection fraction (HFpEF). Banding was evaluated on Changes in metabolism and transcription. Systems biology analysis in a large animal model of HFpEF revealed early cardiac oxidative metabolism alterations at 1 month and persistent skeletal muscle mitochondrial dysfunction at 4 months.