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微小RNA:先天性心脏病与再生中的多效性参与者

MicroRNAs: pleiotropic players in congenital heart disease and regeneration.

作者信息

Hoelscher Sarah C, Doppler Stefanie A, Dreßen Martina, Lahm Harald, Lange Rüdiger, Krane Markus

机构信息

Division of Experimental Surgery, Department of Cardiovascular Surgery, German Heart Center Munich, Technische Universität München, Munich, Germany.

DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.

出版信息

J Thorac Dis. 2017 Mar;9(Suppl 1):S64-S81. doi: 10.21037/jtd.2017.03.149.

Abstract

Congenital heart disease (CHD) is the leading cause of infant death, affecting approximately 4-14 live births per 1,000. Although surgical techniques and interventions have improved significantly, a large number of infants still face poor clinical outcomes. MicroRNAs (miRs) are known to coordinately regulate cardiac development and stimulate pathological processes in the heart, including fibrosis or hypertrophy and impair angiogenesis. Dysregulation of these regulators could therefore contribute (I) to the initial development of CHD and (II) at least partially to the observed clinical outcomes of many CHD patients by stimulating the aforementioned pathways. Thus, miRs may exhibit great potential as therapeutic targets in regenerative medicine. In this review we provide an overview of miR function and elucidate their role in selected CHDs, including hypoplastic left heart syndrome (HLHS), tetralogy of Fallot (TOF), ventricular septal defects (VSDs) and Holt-Oram syndrome (HOS). We then bridge this knowledge to the potential usefulness of miRs and/or their targets in therapeutic strategies for regenerative purposes in CHDs.

摘要

先天性心脏病(CHD)是婴儿死亡的主要原因,每1000例活产中约有4 - 14例受影响。尽管外科技术和干预措施有了显著改善,但仍有大量婴儿面临不良临床结局。已知微小RNA(miR)可协调调节心脏发育,并刺激心脏中的病理过程,包括纤维化或肥大以及损害血管生成。因此,这些调节因子的失调可能(I)导致CHD的初始发展,并且(II)通过刺激上述途径至少部分地导致许多CHD患者观察到的临床结局。因此,miR在再生医学中作为治疗靶点可能具有巨大潜力。在本综述中,我们概述了miR的功能,并阐明了它们在选定的CHD中的作用,包括左心发育不全综合征(HLHS)、法洛四联症(TOF)、室间隔缺损(VSD)和心脏手综合征(HOS)。然后,我们将这些知识与miR和/或其靶点在CHD再生治疗策略中的潜在用途联系起来。

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