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Review
. 2019 Aug 1;127(2):633-644.
doi: 10.1152/japplphysiol.00904.2018. Epub 2018 Dec 20.

Noncoding RNAs regulating cardiac muscle mass

Glenn D Wadley  1 , Séverine Lamon  1 , Sarah E Alexander  1 , Julie R McMullen  2   3   4   5   6 , Bianca C Bernardo  2   3   7
Affiliations
Review

Noncoding RNAs regulating cardiac muscle mass

Glenn D Wadley et al. J Appl Physiol (1985). .

Abstract

Noncoding RNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) play roles in the development and homeostasis of nearly every tissue of the body, including the regulation of processes underlying heart growth. Cardiac hypertrophy can be classified as either physiological (beneficial heart growth) or pathological (detrimental heart growth), the latter of which results in impaired cardiac function and heart failure and is predictive of a higher incidence of death due to cardiovascular disease. Several miRNAs have a functional role in exercise-induced cardiac hypertrophy, while both miRNAs and lncRNAs are heavily involved in pathological heart growth and heart failure. The latter have the potential to act as an endogenous sponge RNA and interact with specific miRNAs to control cardiac hypertrophy, adding another level of complexity to our understanding of the regulation of cardiac muscle mass. In addition to tissue-specific effects, ncRNA-mediated tissue cross talk occurs via exosomes. In particular, miRNAs can be internalized in exosomes and secreted from various cardiac and vascular cell types to promote angiogenesis, as well as protection and repair of ischemic tissues. ncRNAs hold promising therapeutic potential to protect the heart against ischemic injury and aid in regeneration. Numerous preclinical studies have demonstrated the therapeutic potential of ncRNAs, specifically miRNAs, for the treatment of cardiovascular disease. Most of these studies employ antisense oligonucleotides to inhibit miRNAs of interest; however, off-target effects often limit their potential to be translated to the clinic. In this context, approaches using viral and nonviral delivery tools are promising means to provide targeted delivery in vivo.

Keywords: cardiac hypertrophy; heart; lncRNAs; microRNAs; noncoding RNAs.

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Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

Fig. 1.
Fig. 1.
Functional interactions between the different classes of noncoding RNAs (ncRNAs). Long noncoding RNAs (lncRNAs), mRNAs, microRNAs (miRNAs), and circular RNAs (circRNAs) are all transcribed from genomic DNA. lncRNAs and mRNAs can be translated into polypeptides. The green arrows indicate “activation.” The blue lines indicate “inhibition.” Dashed lines indicate that the nature of the interaction is still unknown.
Fig. 2.
Fig. 2.
Schematic of the most prominent and extensively studied noncoding RNAs in physiological and pathological hypertrophy. Increased workload on the heart leads to heart enlargement that is either physiological (due to exercise) or pathological (due to cardiac disease). A number of ncRNAs [microRNAs and long noncoding RNAs (lncRNAs)] have been identified to play important roles in physiological and pathological hypertrophy, of which the most extensively studied are presented. Little is known about the role of lncRNAs and circular RNAs (circRNAs) in physiological hypertrophy, and the role of circRNAs in pathological hypertrophy requires further investigation.
Fig. 3.
Fig. 3.
Exosomal secretion mediates cross-talk between different tissues. Exosomes contain microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and potentially piwi-associated RNAs (piRNAs). When released in cardiomyocytes, these noncoding RNAs have the potential to promote or protect against cardiac hypertrophy.
See this image and copyright information in PMC

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