心脏由细胞成分的异质混合物组成,这些细胞成分完美地混合在一起,能够整合常见的环境信号,以确保适当的心脏功能和性能。代谢定义了一种细胞环境相关的特征,在生存中起着至关重要的作用。扩散,或差异化,作为公认的器官生物学大师,调节体内平衡,疾病进展,和适应组织损伤。心脏是一个要求很高的器官,和成年心肌细胞需要大量的能量来实现足够的收缩力。然而,在氧化线粒体代谢下的功能伴随着有害活性氧的升高,这确实有助于几种心血管疾病的进展,并阻碍哺乳动物心脏的再生能力。心脏代谢在胚胎发育过程中是动态的,并且随着心肌细胞在出生后的第一天成熟和分化而发生实质性变化。在心脏发生的早期阶段,无氧糖酵解是主要的能量程序,而逐渐向氧化磷酸化转变是心肌分化的标志。为了应对心脏损伤,不同的信号通路参与代谢重新连接,以重新激活胚胎生物能量程序或利用替代底物,反映心脏代谢的灵活性及其在器官适应外部因素中的核心作用。尽管胎儿的代谢模式已经确立,新生儿,和成年心肌细胞,我们对其他心脏群体如内皮细胞的生物能量学的了解,心脏成纤维细胞,或者免疫细胞是有限的。考虑到心脏发育过程中和心脏损伤后的紧密细胞间通讯和非自主信号的影响,更好地了解不同心脏细胞的代谢程序,以开发基于代谢重新布线的新介入机会,以预防心力衰竭并改善哺乳动物心脏有限的再生能力,这将是至关重要的。
The heart is composed of a heterogeneous mixture of cellular components perfectly intermingled and able to integrate common environmental signals to ensure proper cardiac function and performance. Metabolism defines a cell context-dependent signature that plays a critical role in survival, proliferation, or differentiation, being a recognized master piece of organ biology, modulating homeostasis, disease progression, and adaptation to tissue damage. The heart is a highly demanding organ, and adult cardiomyocytes require large amount of energy to fulfill adequate contractility. However, functioning under oxidative mitochondrial metabolism is accompanied with a concomitant elevation of harmful reactive oxygen species that indeed contributes to the progression of several cardiovascular pathologies and hampers the regenerative capacity of the mammalian heart. Cardiac metabolism is dynamic along embryonic development and substantially changes as cardiomyocytes mature and differentiate within the first days after birth. During early stages of cardiogenesis, anaerobic glycolysis is the main energetic program, while a progressive switch toward oxidative phosphorylation is a hallmark of myocardium differentiation. In response to cardiac injury, different signaling pathways participate in a metabolic rewiring to reactivate embryonic bioenergetic programs or the utilization of alternative substrates, reflecting the flexibility of heart metabolism and its central role in organ adaptation to external factors. Despite the well-established metabolic pattern of fetal, neonatal, and adult cardiomyocytes, our knowledge about the bioenergetics of other cardiac populations like endothelial cells, cardiac fibroblasts, or immune cells is limited. Considering the close intercellular communication and the influence of nonautonomous cues during heart development and after cardiac damage, it will be fundamental to better understand the metabolic programs in different cardiac cells in order to develop novel interventional opportunities based on metabolic rewiring to prevent heart failure and improve the limited regenerative capacity of the mammalian heart.