Molecular Signature of HFpEF
Andrew Gibb, Emma K. Murray, Deborah Eaton, Anh Tuan Huynh, Dhanendra Tomar, Joanne F. Garbincius, Devin W. Kolmetzky, Remus M. Berretta, Markus Wallner, Steven R. Houser, John W. Elrod
Abstract
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.