Deciphering the Neonatal Cardiac Regenerative Potential and Regulators in Large Animals

摘要 心力衰竭是一种代价高昂且致命的疾病，影响着500多万美国人。成年人的无能 哺乳动物心脏损伤后的再生是心力衰竭病理生理学的核心。我们最近 表明新生哺乳动物的心脏在生命的最初几天能够完全再生 以下是各种类型的受伤情况。尽管它对人类心脏病有重要影响，但仍不清楚。 无论是较大的哺乳动物还是人类都具有这种再生潜力，这一现象将具有显著的 对儿童心脏病和成人心脏病的机制和治疗意义。在目前的提案中，我们 将研究大型哺乳动物中是否存在类似的心脏再生潜力，概述这一过程的持续时间 再生窗，并破译控制心肌细胞周期的调节因子。此外，我们还将审查 我们是否可以修改这些关键的调节因子来控制心肌细胞的细胞周期，从而使心脏重新肌化 有心肌梗死。

ABSTRACT Heart failure is a costly and deadly disease affecting over 5 million Americans. The inability of the adult mammalian heart to regenerate following injury lies at core of the pathophysiology of heart failure. We recently showed that the neonatal mammalian heart is capable of complete regeneration in the first few days of life following various types on injury. Despite the important implications to human heart disease, it is remains unclear whether larger mammals or humans have this regenerative potential, a phenomenon that would have significant mechanistic and therapeutic implications for pediatric as well as adult heart disease. In the current proposal, we will examine whether a similar cardiac regenerative potential exists in large mammals, outline the duration of this regenerative window, and decipher the regulators that controls myocyte cell cycle. In addition, we will examine whether we can modify these key regulators to control the myocytes cell cycle for remuscularization of hearts with myocardial infarction.