Neonatal Heart Responds to Pressure Overload With Differential Alterations in Various Cardiomyocyte Maturation Programs That Accommodate Simultaneous Hypertrophy and Hyperplasia.
Neonatal Heart Responds to Pressure Overload With Differential Alterations in Various Cardiomyocyte Maturation Programs That Accommodate Simultaneous Hypertrophy and Hyperplasia.
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新生儿心脏通过各种心肌细胞成熟程序的差异改变来应对压力过载，以适应同时的肥大和增生。
DOI：
10.3389/fcell.2020.596960
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发表时间：
2020
影响因子：
5.5
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Ding X;Wang S;Wang Y;Yang J;Bao N;Liu J;Zhang Z
压力过载是与右侧先天性心脏病（CHD）相关的病理生理条件之一。患者在出生后就会出现这种情况。然而，关于新生儿心脏对它的反应却知之甚少。我们已经建立了新生大鼠肺动脉带（PAB）模型。本研究表明，PAB加速单核心肌细胞向多核细胞的转变，促进新生儿心脏肥厚生长。后负荷的升高显著提高了新生儿心肌细胞的有丝分裂活性。与增殖潜能一致，压力过载升高也增加了心肌细胞的细胞动力学标志物计数。通过心肌细胞特异性谱系追踪，我们注意到PAB组中罕见的未标记心肌细胞的克隆扩增，揭示了一个具有强大增殖能力的心肌细胞亚群。此外，粘附后第7天的PAB心脏没有巨噬细胞的积累，而巨噬细胞是损伤模型中新生儿心脏再生所必需的免疫反应。转录组学分析显示，新生儿PAB诱导心肌细胞的表达谱，包括心肌细胞肥大，如高度激活的翻译、氧化磷酸化和线粒体生物发生程序等，以及未成熟的心肌细胞，如细胞周期活性和糖酵解代谢增强，细胞骨架和离子通道基因表达下调，维持胎儿特异性的肉瘤亚型等。这表明压力过载对各种心肌细胞成熟（CM）程序有不同的影响，这些程序可能有助于并发心肌细胞肥大和增生。转录谱的二价状态突出了新生儿心肌细胞的可塑性，可以用来适应出生后的环境。
Pressure overload is one of the pathophysiological conditions commonly associated with right-sided congenital heart disease (CHD). Patients suffer from this condition right after birth. However, little is known about how neonatal heart reacts to it. We have previously established a pulmonary artery banding (PAB) model in neonatal rat. Here we show that PAB accelerated transition of mononuclear cardiomyocytes into multinucleated cells to promote hypertrophic growth in neonatal heart. The elevated afterload significantly increased the mitotic activities of neonatal cardiomyocytes. Consistent with the proliferative potential, the elevated pressure overload also increased cytokinetic marker counts of cardiomyocytes. Using cardiomyocyte-specific lineage tracing, we noticed a clonal expansion of rare unlabeled cardiomyocytes in the PAB group, revealing a subgroup of cardiomyocytes with a strong capability of proliferation. In addition, PAB hearts at post-banding day 7 didn’t have the accumulation of macrophages, which is an immune response essential for neonatal heart regeneration in injury models. Transcriptomic analyses revealed that neonatal PAB induced an expression profile featuring both cardiomyocyte hypertrophy, such as highly activated translation, oxidative phosphorylation, and mitochondrial biogenesis programs etc., and immature cardiomyocyte, such as enhanced cell cycle activities and glycolytic metabolism, down-regulated cytoskeleton and ion channel gene expression, and maintenance of fetal-specific sarcomeric isoforms etc. It indicates that pressure overload has differential impacts on various cardiomyocyte maturation (CM) programs that may contribute to the concurrent cardiomyocyte hypertrophy and hyperplasia. The bivalent status of transcriptional profile highlights the plasticity of neonatal cardiomyocytes that can be exploited to adapt the postnatal environment.
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影响因子：
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