Persistent scarring and dilated cardiomyopathy suggest incomplete regeneration of the apex resected neonatal mouse myocardium - A 180 days follow up study
Persistent scarring and dilated cardiomyopathy suggest incomplete regeneration of the apex resected neonatal mouse myocardium - A 180 days follow up study
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DOI：
10.1016/j.yjmcc.2015.11.031
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发表时间：
2016-01-01
影响因子：
5
通讯作者：
Sheikh, Soren Paludan
中科院分区：
文献类型：
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作者：
Andersen, Ditte Caroline;Jensen, Charlotte Harken;Sheikh, Soren Paludan
哺乳动物的心脏损伤通常被认为会导致瘢痕形成，而斑马鱼在心尖切除术（AR）后的中间和可逆的纤维化状态后完全再生心脏。最近，使用AR程序，一天大的小鼠也被认为具有完全的心脏再生能力。相比之下，使用相同的小鼠模型，其他人已经表明再生过程是不完全的，并且在AR后21天仍然存在疤痕。目前的研究测试了这样一种假设，即像斑马鱼一样，新生哺乳动物的纤维化可能是完全心脏再生开始之前的中间反应。通过AR对出生后第1天的C57 BL/6小鼠进行心肌损伤，并在第180天分别使用F-18-氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）和组织学评估心肌功能和疤痕。与假手术小鼠相比，AR小鼠表现出射血分数和室壁运动降低，舒张末期和收缩末期容积增加。瘢痕与胶原蛋白的积累仍然是大量的，增加心脏的大小，而心肌细胞的大小是insufficient.In结论，这些数据表明，心尖切除小鼠的结果在不可逆的纤维化和扩张型心肌病，表明心脏再生是有限的新生哺乳动物，因此不同于在斑马鱼中看到的再生能力。(C)2015爱思唯尔有限公司版权所有。
Heart damage in mammals is generally considered to result in scar formation, whereas zebrafish completely regenerate their hearts following an intermediate and reversible state of fibrosis after apex resection (AR). Recently, using the AR procedure, one-day-old mice were suggested to have full capacity for cardiac regeneration as well. In contrast, using the same mouse model others have shown that the regeneration process is incomplete and that scarring still remains 21 days after AR. The present study tested the hypothesis that like in zebrafish, fibrosis in neonatal mammals could be an intermediate response before the onset of complete heart regeneration. Myocardial damage was performed by AR in postnatal day 1 C57BL/6 mice, and myocardial function and scarring assessed at day 180 using F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) and histology, respectively. AR mice exhibited decreased ejection fraction and wall motion with increased end-diastolic and systolic volumes compared to sham-operated mice. Scarring with collagen accumulation was still substantial, with increased heart size, while cardiomyocyte size was unaffected.In conclusion, these data thus show that apex resection in mice results in irreversible fibrosis and dilated cardiomyopathy suggesting that cardiac regeneration is limited in neonatal mammals and thus distinct from the regenerative capacity seen in zebrafish. (C) 2015 Elsevier Ltd. All rights reserved.