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微小RNA:心脏发育与疾病中的新型调控因子

MicroRNAs: novel regulators in cardiac development and disease.

作者信息

Thum Thomas, Catalucci Daniele, Bauersachs Johann

机构信息

Medizinische Klinik und Poliklinik I, Universitätsklinikum, Julius-Maximilians-Universität, Josef-Schneider-Street 2, D-97080 Würzburg, Germany.

出版信息

Cardiovasc Res. 2008 Sep 1;79(4):562-70. doi: 10.1093/cvr/cvn137. Epub 2008 May 29.

Abstract

MicroRNAs (miRNAs) are endogenous, small ribonucleotides regulating the translation of target messenger RNAs that have been shown to be involved in orchestrating growth, development, function, and stress responses of various organs, including the heart. Muscle miRNAs are mainly controlled by a network of myogenic transcription factors, and throughout cardiac development they fine-tune regulatory protein levels in a spatiotemporal manner. Recent profiling studies revealed that miRNA expression patterns are derailed in both human cardiac disease and animal models of cardiac hypertrophy and failure. Modulation of miRNA expression in vitro as well as in vivo has revealed an important role of miRNAs in regulating heart function, particularly cardiac growth and conductance. Here, we overview the recent findings on miRNAs in cardiac development and disease and report the latest advances in the identification and validation of miRNA targets, which are important for a comprehensive understanding of cardiac miRNA function. Finally, we focus on the development and use of miRNA antagonists (antagomirs) to target miRNAs in vivo, which may translate into novel therapeutic strategies for heart disease in the future.

摘要

微小RNA(miRNA)是内源性小核糖核苷酸,可调节靶信使核糖核酸的翻译,已证明其参与协调包括心脏在内的各种器官的生长、发育、功能和应激反应。肌肉miRNA主要受成肌转录因子网络控制,在整个心脏发育过程中,它们以时空方式微调调节蛋白水平。最近的分析研究表明,在人类心脏疾病以及心脏肥大和衰竭的动物模型中,miRNA表达模式均出现紊乱。体外和体内对miRNA表达的调节已揭示了miRNA在调节心脏功能,特别是心脏生长和传导方面的重要作用。在此,我们概述了关于miRNA在心脏发育和疾病方面的最新研究发现,并报告了miRNA靶标的鉴定和验证方面的最新进展,这对于全面理解心脏miRNA功能很重要。最后,我们重点介绍了miRNA拮抗剂(抗miR)在体内靶向miRNA的开发和应用,这可能在未来转化为心脏病的新型治疗策略。

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