Heart failure is a devastating disease that affects more than 26 million individuals worldwide and has a 5-year survival rate of less than 50%, with its development in part reflecting the inability of the adult mammalian heart to regenerate damaged myocardium. In contrast, certain vertebrate species including fish and amphibians, as well as neonatal mammals, are capable of complete cardiac regeneration after various types of myocardial injury such as resection of the ventricular apex or myocardial infarction, with this regeneration being mediated by the proliferation of cardiomyocytes, dissolution of temporary fibrosis, and revascularization of damaged tissue. In an effort to identify regulators of cardiac regeneration and to develop novel therapeutic strategies for induction of myocardial regeneration in the adult human heart, recent studies have adopted an approach based on comparative biology. These studies have pointed to cellular or tissue responses to environmental cues-including activation of the immune system, the reaction to mechanical stress, and the adoption of oxidative metabolism-as key determinants of whether the heart undergoes regeneration or nonregenerative scar formation after injury. We here summarize recent insight into the molecular mechanisms as well as environmental and systemic factors underlying cardiac regeneration based on the findings of inter- or intraspecific comparisons between regenerative and nonregenerative responses to heart injury. We also discuss how recent progress in understanding the molecular, systemic, and environmental basis of cardiac regeneration in a variety of organisms may relate to multiple scientific fields including ecology, evolutionary as well as developmental biology.

中文翻译：

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心脏再生是对环境的适应。

心力衰竭是一种毁灭性疾病，在全球范围内影响超过2600万人，其5年生存率不到50％，其发展在一定程度上反映了成年哺乳动物心脏无法再生受损心肌的能力。相反，某些鱼类，包括鱼类和两栖动物，以及新生哺乳动物，在各种类型的心肌损伤（例如切除心尖或心肌梗塞）后能够完成心脏再生，这种再生是由心肌细胞的增殖介导的。 ，暂时性纤维化的溶解以及受损组织的血运重建。为了确定心脏再生的调节剂，并开发出新颖的治疗策略来诱导成人心脏中的心肌再生，最近的研究采用了一种基于比较生物学的方法。这些研究指出细胞或组织对环境线索的反应，包括免疫系统的激活，对机械压力的反应以及氧化代谢的采用，是决定心脏受伤后是否经历再生或非再生性疤痕形成的关键因素。我们在此基于对心脏损伤的再生和非再生反应之间的种间或种内比较的发现，总结了对心脏再生的分子机制以及环境和系统性因素的最新见解。我们还将讨论在了解分子，系统，