Research Paper Volume 12, Issue 4 pp 3388—3406
Cell-to-cell lactate shuttle operates in heart and is important in age-related heart failure
- 1 Department of Molecular Physiology and Neurobiology, University of Wrocław, Wrocław 50-137, Poland
- 2 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
received: October 18, 2019 ; accepted: January 27, 2020 ; published: February 8, 2020 ;https://doi.org/10.18632/aging.102818
How to Cite
Copyright © 2020 Gizak et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Recent studies have revealed a resemblance of a HIF-regulated heart and brain glycolytic profiles prompting the hypothesis that the classical cell-to-cell lactate shuttle observed between astrocytes and neurons operates also in heart – between cardiac fibroblasts and cardiomyocytes. Here, we demonstrate that co-culturing of cardiomyocytes with cardiac fibroblasts leads to orchestrated changes in expression and/or localization pattern of glucose metabolism enzymes and lactate transport proteins in both cell types. These changes are regulated by paracrine signaling using microvesicle-packed and soluble factors released to the culture medium and, taken together, they concur with the cardiac lactate shuttle hypothesis. The results presented here show that similarity of heart and brain proteomes demonstrated earlier extend to physiological level and provide a theoretical rationale for designing novel therapeutic strategies for treatment of cardiomyopathies resulting from disruption of the maturation of cardiac metabolic pathways, and of heart failure associated with metabolic complications and age-related heart failure linked with extracellular matrix deposition and hypoxia.