Cardiac disease is the main cause of death worldwide. Insufficient regeneration of the adult mammalian heart is a major driver of cardiac morbidity and mortality. Cardiac regeneration occurs in early postnatal mice, thus understanding mechanisms of mammalian cardiac regeneration could facilitate the development of novel therapeutic strategies. Here, we provide a detailed description of a neonatal mouse model of pressure overload by transverse aortic constriction (nTAC) that can be applied at postnatal days 1 and 7. We have previously used this model to demonstrate that mice are able to fully adapt to pressure overload following nTAC on postnatal day 1. In contrast, when nTAC is applied in the non-regenerative phase (at postnatal day 7), it is associated with a maladaptive response similar to that seen when transverse aortic constriction (TAC) is applied to adult mice. Once a user is experienced in nTAC surgery, the procedure can be completed in less than 10 min per mouse. We anticipate that this model will facilitate the discovery of therapeutic targets to treat patients or prevent pressure overload-induced cardiac failure in the future.

心脏疾病是全球范围内主要的死亡原因。成年哺乳动物心脏的再生不足是心脏发病率和死亡率的主要驱动力。心脏再生发生在出生后的早期小鼠中，因此了解哺乳动物心脏再生的机制可以促进新型治疗策略的发展。在这里，我们提供了可以在出生后的第1天和第7天应用的横向小鼠主动脉缩窄（nTAC）引起的压力超负荷的新生小鼠模型的详细描述。我们先前已使用该模型来证明小鼠能够完全适应压力出生后第1天在nTAC之后出现超负荷。相反，在非再生阶段（出生后第7天）应用nTAC时，它与适应不良反应有关，类似于成年小鼠应用横向主动脉缩窄（TAC）时的反应。一旦用户经历过nTAC手术，每只小鼠只需不到10分钟即可完成该过程。我们预计该模型将有助于将来发现治疗靶标或预防压力超负荷引起的心力衰竭的治疗靶标。