Find the stimulus, save the heart: a heroes' story.
Find the stimulus, save the heart: a heroes' story.
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找到刺激，拯救心灵：英雄的故事。
DOI：
10.1152/ajpheart.00194.2021
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
DeLeon-Pennell,KristineY
中科院分区：
文献类型：
--
作者：
Westbury,Baylee;Bolus,Dawson;DeLeon-Pennell,KristineY
心肌梗死（MI）仍然是世界范围内最常见的心力衰竭原因(1)。出生第一周后，心肌细胞无法再生，缺血损伤后，心脏发生纤维化重构。作为对缺血事件的反应，包括巨噬细胞在内的免疫细胞开始清除坏死碎片并刺激富含细胞外基质（ECM）的疤痕沉积(2)。最近的转录组学分析表明，随着年龄的增长，新生儿卵黄囊巨噬细胞向经典巨噬细胞的转变刺激了心肌梗死后基于成纤维细胞的不良心脏重构。卵黄囊来源的巨噬细胞在新生儿心脏中占主导地位，更容易接受影响心肌细胞再生的生长因子。控制年龄变化和通过炎症驱动纤维化的分子机制尚不清楚。在这一期的《美国生理学-心脏与循环生理学杂志》上，Whitehead等人(3)强化了巨噬细胞和心脏成纤维细胞之间的串音机制，并利用来自多个数据集的基因组数据探讨了该机制如何促进心肌梗死后的心脏重塑。通过对梗死前后再生（P1）和非再生（P8）小鼠心脏的转录组学分析，他们发现控制损伤相关分子模式（DAMP）信号、ECM沉积和趋化因子谱的基因表达存在差异。这项研究的一个主要优势是分析了心脏损伤和愈合的许多变量。因为这些过程是多因素的，所以考虑多个影响变量是很重要的。有趣的是，P1和P8心脏在梗死后立即具有相似的表达谱，但P1心脏最终恢复到基线，而P8心脏形成了新的稳态基线。由此得出结论，与非再生（P8）心脏相比，再生（P1）心脏中信号换能器和转录激活因子3 （STAT3）信号传导发生得更早，导致炎症消退和白细胞募集减少。
Myocardial infarction (MI) remains the most common cause for heart failure worldwide (1). After the first week of birth, cardiomyocytes are unable to regenerate, and after ischemic injury, the heart undergoes fibrotic remodeling. In response to the ischemic event, immune cells, including macrophages, begin to remove the necrotic debris and stimulate deposition of an extracellular matrix (ECM)-rich scar (2). Recent transcriptomic analyses have suggested that with age, the transition from neonatal yolk sac macrophages to classical macrophages is stimulating adverse fibroblast-based cardiac remodeling after MI. Yolk sac-derived macrophages predominate in the neonate hearts and are more receptive to growth factors that affect cardiomyocyte regeneration. The molecular mechanisms that govern the change with age and drive fibrosis via inflammation are poorly understood.In this issue of the American Journal of Physiology-Heart and Circulatory Physiology, Whitehead et al.(3) potentiated the cross talk mechanisms that occur between macrophages and cardiac fibroblasts and explore how this mechanism contributes to heart remodeling after MI injury using genomic data from multiple data sets. Through transcriptomic analysis of regenerative (P1) and nonregenerative (P8) mouse hearts before and after infarction, they found differences in expression of genes that control damage-associated molecular pattern (DAMP) signaling, ECM deposition, and chemokine profiles. A major strength of this study is the analysis of the many variables of cardiac injury and healing. Because these processes are multifactorial, it is important to account for the multiple affecting variables. Interestingly, the P1 and P8 hearts had similar expression profiles immediately after infarct, but the P1 hearts eventually returned to baseline whereas the P8 hearts formed a new homeostatic baseline. This led to the conclusion that signal transducer and activator of transcription 3 (STAT3) signaling occurs earlier in the regenerative (P1) hearts resulting in resolution of inflammation and an attenuation in leukocyte recruitment compared with the nonregenerating (P8) hearts.