| First Author | Aksentijević D | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 4337 |
| PubMed ID | 32859897 | Mgi Jnum | J:303345 |
| Mgi Id | MGI:6471323 | Doi | 10.1038/s41467-020-18160-x |
| Citation | Aksentijevic D, et al. (2020) Intracellular sodium elevation reprograms cardiac metabolism. Nat Commun 11(1):4337 |
| abstractText | Intracellular Na elevation in the heart is a hallmark of pathologies where both acute and chronic metabolic remodelling occurs. Here, we assess whether acute (75 muM ouabain 100 nM blebbistatin) or chronic myocardial Nai load (PLM(3SA) mouse) are causally linked to metabolic remodelling and whether the failing heart shares a common Na-mediated metabolic 'fingerprint'. Control (PLM(WT)), transgenic (PLM(3SA)), ouabain-treated and hypertrophied Langendorff-perfused mouse hearts are studied by (23)Na, (31)P, (13)C NMR followed by (1)H-NMR metabolomic profiling. Elevated Nai leads to common adaptive metabolic alterations preceding energetic impairment: a switch from fatty acid to carbohydrate metabolism and changes in steady-state metabolite concentrations (glycolytic, anaplerotic, Krebs cycle intermediates). Inhibition of mitochondrial Na/Ca exchanger by CGP37157 ameliorates the metabolic changes. In silico modelling indicates altered metabolic fluxes (Krebs cycle, fatty acid, carbohydrate, amino acid metabolism). Prevention of Nai overload or inhibition of Na/Camito may be a new approach to ameliorate metabolic dysregulation in heart failure. |
