Department of Molecular Physiology and Neurobiology, University of Wrocław, Wrocław 50-137, Poland.
Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA.
Aging (Albany NY). 2020 Feb 8;12(4):3388-3406. doi: 10.18632/aging.102818.
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.
最近的研究揭示了 HIF 调节的心脏和大脑糖酵解特征的相似性，这促使人们假设在星形胶质细胞和神经元之间观察到的经典细胞间乳酸穿梭也存在于心脏中 - 在心脏成纤维细胞和心肌细胞之间。在这里，我们证明了心肌细胞与心脏成纤维细胞共培养会导致两种细胞类型中葡萄糖代谢酶和乳酸转运蛋白的表达和/或定位模式的协调变化。这些变化受微泡包封和分泌到培养基中的可溶性因子的旁分泌信号调节，并且它们共同符合心脏乳酸穿梭假说。这里呈现的结果表明，早期证明的心脏和大脑蛋白质组的相似性扩展到生理水平，并为设计用于治疗由于心脏代谢途径成熟中断以及与代谢并发症相关的心力衰竭和与细胞外基质沉积和缺氧相关的年龄相关心力衰竭导致的心肌病的新型治疗策略提供了理论依据。
