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聚焦心脏再生中的表观遗传重编程。

Spotlight on epigenetic reprogramming in cardiac regeneration.

机构信息

Heart Failure and Cardiac Regeneration (ICREC) Research Program, Health Science Research Institute Germans Trias i Pujol (IGTP), Carretera Canyet, s/n, Camí de les Escoles, s/n, 08916, Badalona, Spain; CIBERCV, Instituto de Salud Carlos III, Av. de Monforte de Lemos, 5, 28029, Madrid, Spain.

Genetics and Epigenetics of Cancer Research Program, Health Science Research Institute Germans Trias i Pujol (IGTP), Carretera Canyet, s/n, Camí de les Escoles, s/n, 08916, Badalona, Spain; Serra-Hunter Professor at Department of Pathology and Experimental Therapeutics, School of Medicine, Health Science Campus of Bellvitge, University of Barcelona, Carrer de la Feixa Llarga, s/n, Hospitalet de Llobregat, Barcelona, 08907, Spain.

出版信息

Semin Cell Dev Biol. 2020 Jan;97:26-37. doi: 10.1016/j.semcdb.2019.04.009. Epub 2019 Apr 26.

Abstract

Heart failure of ischemic origin is caused by the presence of a large scar resulting from an acute myocardial infarction. Acute myocardial infarction generally occurs when blood supply to the heart is blocked. Regenerative strategies that limit infarct injury would be able to prevent adverse post-ischemic remodelling and maintain the structural support necessary for effective cardiomyocyte contraction. Our understanding of endogenous cardiac regeneration and its biology has exposed a variety of targets for therapeutic approaches, such as non-coding RNAs, DNA methylation, histone modifications, direct cardiac reprogramming, cell transplantation, stimulation of resident cardiomyocytes, proliferation, and inhibition of cardiomyocyte death. In this review, we address the epigenetic mechanisms underlying these strategies and the use of therapeutic epigenetic molecules or epidrugs.

摘要

缺血性起源的心力衰竭是由急性心肌梗死导致的大瘢痕引起的。急性心肌梗死通常发生在心脏供血被阻断时。限制梗死损伤的再生策略能够预防缺血后不良重构,并维持有效心肌细胞收缩所需的结构支撑。我们对内源性心脏再生及其生物学的理解已经揭示了多种治疗方法的靶点,如非编码 RNA、DNA 甲基化、组蛋白修饰、直接心脏重编程、细胞移植、刺激驻留心肌细胞、增殖和抑制心肌细胞死亡。在这篇综述中,我们讨论了这些策略背后的表观遗传机制以及治疗性表观遗传分子或表药物的应用。

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