Molecular Signature of HFpEF
| Autor: | John W. Elrod, Steven R. Houser, Markus Wallner, Remus M. Berretta, Dhanendra Tomar, Anh T Huynh, Joanne F Garbincius, Deborah M Eaton, Emma K Murray, Devin W. Kolmetzky, Andrew A. Gibb |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
MS/MS
tandem mass spectrometry FDR false discovery rate Systems biology ETC electron transport chain heart failure HFpEF heart failure with preserved ejection fraction Mitochondrion Biology HF heart failure UPLC ultraperformance liquid chromatography Transcriptome transcriptomics Metabolomics medicine EF ejection fraction LA left atrial LAV left atrial volume m/z mass to charge ratio HFrEF heart failure with reduced ejection fraction GO gene ontology Maladaptation ESI electrospray ionization LV left ventricle/ventricular Skeletal muscle systems biology FC fold change medicine.disease metabolomics preserved ejection fraction ECM extracellular matrix Cell biology mitochondria BCAA branched chain amino acids medicine.anatomical_structure RI retention index Heart failure Preclinical Research RCR respiratory control ratio Cardiology and Cardiovascular Medicine Heart failure with preserved ejection fraction DAG diacylglycerol |
| Zdroj: | JACC: Basic to Translational Science |
| ISSN: | 2452-302X |
| DOI: | 10.1016/j.jacbts.2021.07.004 |
| Popis: | Visual Abstract Highlights • Early cardiac mitochondrial dysfunction is mediated by transcriptional down-regulation of the mitochondrial proteome. • Comprehensive metabolic remodeling is conserved throughout HFpEF progression and includes increased amino acid and lipid species, indicative of impaired oxidative metabolism. • Transcriptional and metabolic remodeling of skeletal muscle suggests cardiac signaling as a mediator of peripheral tissue maladaptation. • Unbiased systems-level analysis provides new mechanisms underlying HFpEF development. Summary 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. |
| Databáze: | OpenAIRE |
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