利用胎儿和成人基因重编程治疗心脏病。
Harnessing fetal and adult genetic reprograming for therapy of heart disease.
作者信息
Nandi Shyam Sundar, Mishra Paras Kumar
机构信息
Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA ; Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
出版信息
J Nat Sci. 2015 Apr;1(4).
Heart is the first organ formed during organogenesis. The fetal heart undergoes several structural and functional modifications to form the four-chambered mammalian heart. The adult heart shows different adaptations during compensatory and decompensatory heart failure. However, one common adaptation in the pathological heart is fetal reprogramming, where the adult heart expresses several genes and miRNAs which are active in the fetal stage. The fetal reprogramming in the failing heart raises several questions, such as whether the switch of adult to fetal genetic programming is an adaptive response to cope with adverse remodeling of the heart, does the expression of fetal genes protect the heart during compensatory and/or decompensatory heart failure, does repressing the fetal gene in the failing heart is protective to the heart? To answer these questions, we need to understand the expression of genes and miRNAs that are reprogrammed in the failing heart. In view of this, we provided an overview of differentially expressed genes and miRNAs, and their regulation in this review. Further, we elaborated novel strategies for a plausible future therapy of cardiovascular diseases.
心脏是器官发生过程中形成的第一个器官。胎儿心脏会经历几次结构和功能上的改变，以形成四腔的哺乳动物心脏。成体心脏在代偿性和失代偿性心力衰竭期间表现出不同的适应性变化。然而，病理性心脏中一个常见的适应性变化是胎儿重编程，即成年心脏表达一些在胎儿阶段活跃的基因和微小RNA（miRNA）。衰竭心脏中的胎儿重编程引发了几个问题，比如从成年基因程序转换为胎儿基因程序是否是一种应对心脏不良重塑的适应性反应，胎儿基因的表达在代偿性和/或失代偿性心力衰竭期间是否能保护心脏，在衰竭心脏中抑制胎儿基因对心脏是否有保护作用？为了回答这些问题，我们需要了解在衰竭心脏中发生重编程的基因和miRNA的表达情况。鉴于此，我们在本综述中概述了差异表达的基因和miRNA及其调控。此外，我们阐述了未来治疗心血管疾病的合理新策略。
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