Background. Pediatric patients show an impressive capacity of cardiac regeneration. In contrast, severely deteriorated adult hearts do usually not recover. Since cardiac remodeling—involving the expression of fetal genes—is regarded as an adaptation to stress, we compared hearts of adult patients suffering from dilated cardiomyopathy (DCM) with remodeling of cultured neonatal (NRC) as well as adult (ARC) rat cardiomyocytes and the developing postnatal myocardium. Methods. NRC and ARC were stimulated with serum and cardiac morphogens derived from DCM hearts. Protein synthesis (PS) as well as protein accumulation (PA) was measured, and cell survival was determined under ischemic conditions. Fetal markers were investigated by Western blot. Biomarkers of remodeling were analyzed in controls, DCM, and 2- to 6-month-old children with tetralogy of Fallot as well as in neonatal and adult rats by immunofluorescence. Results. In NRC, serum and morphogens strongly stimulated PS and PA and the reestablishment of cell-cell contacts (CCC). In ARC, both stimulants increased PS and CCC, but PA was only elevated after serum stimulation. In contrast to serum, morphogen treatment resulted in the expression of fetal genes in ARC as determined by nonmuscle α-actinin-1 and α-actinin-4 expression (NM-actinins) and was associated with increased survival under ischemia. NM-actinins were present in cardiomyocytes of DCM in a cross-striated pattern reminiscent of sarcomeres as well as in extensions of the area of the intercalated disc (ID). NM-actinins are expressed in NRC and in the developing heart. Radixin staining revealed remodeling of the area of the ID in DCM almost identical to stimulated cultured ARC. Conclusions. Remodeling was similar in ARC and in cardiomyocytes of DCM suggesting evolutionary conserved mechanisms of regeneration. Despite activation of fetal genes, the atrophy of ARC indicates differences in their regenerative capacity from NRC. Cardiac-derived factors induced NM-actinin expression and increased survival of ischemic ARC while circulating molecules were less effective. Identification of these cardiac-derived factors and determination of their individual capacity to heal or damage are of particular importance for a biomarker-guided therapy in adult patients.

中文翻译：

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Radixin重定位和非肌肉α-肌动蛋白表达是扩张型心肌病成年患者心肌细胞重塑的特征。

背景。儿科患者表现出令人印象深刻的心脏再生能力。相反，严重恶化的成人心脏通常不会恢复。由于涉及胎儿基因表达的心脏重塑被认为是对压力的适应，我们将患有扩张型心肌病 (DCM) 的成年患者的心脏与培养的新生儿 (NRC) 以及成年 (ARC) 大鼠心肌细胞的重塑进行了比较，发育中的出生后心肌。方法. 用源自 DCM 心脏的血清和心脏形态发生素刺激 NRC 和 ARC。测量蛋白质合成 (PS) 以及蛋白质积累 (PA)，并在缺血条件下确定细胞存活率。通过蛋白质印迹研究胎儿标志物。通过免疫荧光分析了对照组、DCM 和 2 至 6 个月大的法洛四联症儿童以及新生和成年大鼠的重塑生物标志物。结果。在 NRC 中，血清和形态发生素强烈刺激 PS 和 PA 以及细胞-细胞接触 (CCC) 的重建。在 ARC 中，两种兴奋剂均增加 PS 和 CCC，但 PA 仅在血清刺激后升高。与血清相比，形态发生素处理导致 ARC 中胎儿基因的表达，由非肌肉α确定-actinin-1 和α -actinin-4 表达 (NM-actinins) 与缺血下存活率增加有关。NM-肌动蛋白以交叉条纹模式存在于 DCM 的心肌细胞中，让人联想到肌节以及闰盘 (ID) 区域的扩展。NM-肌动蛋白在 NRC 和发育中的心脏中表达。Radixin 染色显示 DCM 中 ID 区域的重塑与受刺激的培养 ARC 几乎相同。结论. ARC 和 DCM 心肌细胞的重塑相似，表明再生的进化保守机制。尽管激活了胎儿基因，但 ARC 的萎缩表明它们与 NRC 的再生能力存在差异。心脏衍生因子诱导 NM-actinin 表达并增加缺血性 ARC 的存活率，而循环分子的效果较差。识别这些心脏衍生因素并确定它们的个体愈合或损伤能力对于成人患者的生物标志物指导治疗特别重要。