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  • Review Article
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Noncoding RNAs and myocardial fibrosis

Nature Reviews Cardiology volume 11, pages 655–663 (2014)Cite this article

Subjects

Key Points

  • Cardiac fibrosis is an important event of the cardiac remodelling process, which includes activation of fibroblasts and exaggerated extracellular matrix production

  • Noncoding RNAs (ncRNAs) are important cellular regulators and divided into several classes, such as small microRNAs (∼22 nucleotides) and long noncoding RNAs (>200 nucleotides)

  • ncRNAs are detectable in blood and other body fluids and can be used for improved diagnosis of cardiac diseases including cardiac remodelling

  • ncRNAs provide powerful therapeutic targets that can be modulated in vivo by injection of specific oligonucleotides to repress cardiac diseases including the cardiac fibrosis process

  • Paracrine signalling and cell–cell interactions have a major role during cardiac remodelling, and ncRNAs can contribute to this process by active cellular secretion and uptake mechanisms within the cardiovascular environment

Abstract

Cardiac stress leads to remodelling of cardiac tissue, which often progresses to heart failure and death. Part of the remodelling process is the formation of fibrotic tissue, which is caused by exaggerated activity of cardiac fibroblasts leading to excessive extracellular matrix production within the myocardium. Noncoding RNAs (ncRNAs) are a diverse group of endogenous RNA-based molecules, which include short (∼22 nucleotides) microRNAs and long ncRNAs (of >200 nucleotides). These ncRNAs can regulate important functions in many cardiovascular cells types. This Review focuses on the role of ncRNAs in cardiac fibrosis; specifically, ncRNAs as therapeutic targets, factors for direct fibroblast transdifferentation, their use as diagnostic and prognostic markers, and their potential to function as paracrine modulators of cardiac fibrosis and remodelling.

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Figure 1: ncRNAs in fibroblast biology.
Figure 2: ncRNAs in transdifferentiation of fibroblasts towards cardiomyocytes.
Figure 3: Cardiac fibroblasts involved in intercellular communication.

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Acknowledgements

T.T. acknowledges support from the European Commission-funded FIBROTARGET project, the Integrated Research and Treatment Centre Transplantation (grant number 01EO1302), and Fondation Leducq (Project MIRVAD).

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  1. Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl Neuberg Strasse 1, Hannover, 30625, Germany

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T.T. declares that he holds patents relating to the diagnostic and therapeutic use of ncRNAs in cardiovascular diseases.

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Thum, T. Noncoding RNAs and myocardial fibrosis. Nat Rev Cardiol 11, 655–663 (2014). https://doi.org/10.1038/nrcardio.2014.125

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