Deciphering the Neonatal Cardiac Regenerative Potential and Regulators in Large Animals

破译大型动物的新生儿心脏再生潜力和调节器

基本信息

批准号：
10207761
负责人：
Hesham Sadek
金额：
$ 62.41万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-15 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10207761
关键词：
Adult Affect American Animals Apical Birth CHEK2 gene Cardiac Cardiac Myocytes Cell Aging Cell Cycle Cell Cycle Arrest Cell Cycle Progression Cell Respiration Cells Childhood DNA Damage DNA-PKcs Dependovirus Disease Enhancers Ensure Environment Excision Family suidae Functional disorder Heart Heart Diseases Heart failure Human Injury Label Left Life Mammals Measures Mediating Mitochondria Monitor Muscle Cells Myocardial Myocardial Infarction Myocardium Natural regeneration Neonatal Newborn Infant Oxygen Pathologic Phosphotransferases Production RNA Reactive Oxygen Species Recovery Recovery of Function Regenerative capacity Regulation Reporting Rodent Role Signal Transduction Testing Therapeutic Time Transfection Ventricular base congenital heart disorder cost experimental study genome integrity heart function inhibitor/antagonist ischemic injury knock-down myocardial injury neonatal mice oxidative DNA damage postnatal promoter regeneration potential regenerative response stem cells

项目摘要

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.

抽象的心力衰竭是一种昂贵且致命的疾病，影响着超过 500 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。我们最近研究表明，新生哺乳动物的心脏能够在生命的最初几天内完全再生以下是关于伤害的各种类型。尽管对人类心脏病有重要影响，但仍不清楚无论大型哺乳动物还是人类都具有这种再生潜力，这种现象将产生重大影响对儿科和成人心脏病的机制和治疗意义。在当前的提案中，我们将检查大型哺乳动物是否存在类似的心脏再生潜力，概述这种情况的持续时间再生窗口，并破译控制心肌细胞周期的调节因子。此外，我们将检查我们是否可以修改这些关键调节因子来控制心肌细胞的细胞周期，从而实现心脏的再肌化患有心肌梗塞。