Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD 21205, USA.
Department of Cell and Regenerative Biology, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53705, USA.
Semin Cell Dev Biol. 2021 Oct;118:136-143. doi: 10.1016/j.semcdb.2021.03.026. Epub 2021 Apr 28.
The heart undergoes profound morphological and functional changes as it continues to mature postnatally. However, this phase of cardiac development remains understudied. More recently, cardiac maturation research has attracted a lot of interest due to the need for more mature stem cell-derived cardiomyocytes for disease modeling, drug screening and heart regeneration. Additionally, neonatal heart injury models have been utilized to study heart regeneration, and factors regulating postnatal heart development have been associated with adult cardiac disease. Critical components of cardiac maturation are systemic and local biochemical cues. Specifically, cardiac innervation and the concentration of various metabolic hormones appear to increase perinatally and they have striking effects on cardiomyocytes. Here, we first report some of the key parameters of mature cardiomyocytes and then discuss the specific effects of neurons and hormonal cues on cardiomyocyte maturation. We focus primarily on the structural, electrophysiologic, metabolic, hypertrophic and hyperplastic effects of each factor. This review highlights the significance of underappreciated regulators of cardiac maturation and underscores the need for further research in this exciting field.
心脏在出生后继续发育成熟的过程中会经历深刻的形态和功能变化。然而，这一心脏发育阶段的研究仍相对较少。最近，由于需要更成熟的干细胞来源的心肌细胞用于疾病建模、药物筛选和心脏再生，心脏成熟研究引起了广泛关注。此外，新生儿心脏损伤模型已被用于研究心脏再生，调节出生后心脏发育的因素与成人心脏疾病有关。心脏成熟的关键组成部分是全身和局部的生化线索。具体来说，心脏神经支配和各种代谢激素的浓度似乎在围产期增加，对心肌细胞有显著影响。在这里，我们首先报告一些成熟心肌细胞的关键参数，然后讨论神经元和激素线索对心肌细胞成熟的具体影响。我们主要关注每个因素对心肌细胞的结构、电生理、代谢、肥大和增生的影响。本综述强调了心脏成熟中被低估的调节因子的重要性，并强调了在这个令人兴奋的领域进一步研究的必要性。
