Intracellular sodium elevation reprograms cardiac metabolism.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32859897.
- Also identified by DOI 10.1038/s41467-020-18160-x and PMC identifier 7455741.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 μM ouabain 100 nM blebbistatin) or chronic myocardial Na<sub>i</sub> load (PLM<sup>3SA</sup> mouse) are causally linked to metabolic remodelling and whether the failing heart shares a common Na-mediated metabolic 'fingerprint'. Control (PLM<sup>WT</sup>), transgenic (PLM<sup>3SA</sup>), ouabain-treated and hypertrophied Langendorff-perfused mouse hearts are studied by <sup>23</sup>Na, <sup>31</sup>P, <sup>13</sup>C NMR followed by <sup>1</sup>H-NMR metabolomic profiling. Elevated Na<sub>i</sub> 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 Na<sub>i</sub> overload or inhibition of Na/Ca<sub>mito</sub> may be a new approach to ameliorate metabolic dysregulation in heart failure.
Medical subject headings
- Cellular Reprogramming
- Cytoplasm
- Heart Failure
- Myocardium
- Sodium