Metabolic remodeling plays an important role in the pathophysiology of heart failure (HF). We sought to characterize metabolic remodeling and implicated signaling pathways in two rat models of early systolic dysfunction (MOD), and overt systolic HF (SHF). Tandem mass tag-labeled shotgun proteomics, phospho-(p)-proteomics, and non-targeted metabolomics analyses were performed in left ventricular myocardium tissue from Sham, MOD, and SHF using liquid chromatography–mass spectrometry, n = 3 biological samples per group. Mitochondrial proteins were predominantly down-regulated in MOD (125) and SHF (328) vs. Sham. Of these, 82% (103/125) and 66% (218/328) were involved in metabolism and respiration. Oxidative phosphorylation, mitochondrial fatty acid β-oxidation, Krebs cycle, branched-chain amino acids, and amino acid (glutamine and tryptophan) degradation were highly enriched metabolic pathways that decreased in SHF > MOD. Glycogen and glucose degradation increased predominantly in MOD, whereas glycolysis and pyruvate metabolism decreased predominantly in SHF. PKA signaling at the endoplasmic reticulum–mt interface was attenuated in MOD, whereas overall PKA and AMPK cellular signaling were attenuated in SHF vs. Sham. In conclusion, metabolic remodeling plays an important role in myocardial remodeling. PKA and AMPK signaling crosstalk governs metabolic remodeling in progression to SHF.
Bibliographical noteFunding Information:
Funding: This work was supported by an internal grant award to A.H.C., and the Carol Lavin Bernick Faculty Grant award to A.H.C.; an NIH/NHLBI R01-HL070241 grant award to P.D.; NIH HL-148836, and NIH AG-063345 grant awards to D.W.B., and the Louisiana Board of Regents Endowed Chairs for Eminent Scholars program to D.W.B.
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
- Calcium cycling
- Heart failure
- Metabolic remodeling
PubMed: MeSH publication types
- Journal Article