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  • Review Article
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Long non-coding RNAs in cardiac hypertrophy and heart failure: functions, mechanisms and clinical prospects

Nature Reviews Cardiology volume 21, pages 326–345 (2024)Cite this article

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Abstract

The surge in reports describing non-coding RNAs (ncRNAs) has focused attention on their possible biological roles and effects on development and disease. ncRNAs have been touted as previously uncharacterized regulators of gene expression and cellular processes, possibly working to fine-tune these functions. The sheer number of ncRNAs identified has outpaced the capacity to characterize each molecule thoroughly and to reliably establish its clinical relevance; it has, nonetheless, created excitement about their potential as molecular targets for novel therapeutic approaches to treat human disease. In this Review, we focus on one category of ncRNAs — long non-coding RNAs — and their expression, functions and molecular mechanisms in cardiac hypertrophy and heart failure. We further discuss the prospects for this specific class of ncRNAs as novel targets for the diagnosis and treatment of these conditions.

Key points

  • Long non-coding RNAs (lncRNAs) are a class of non-coding RNA that can regulate gene expression at multiple levels, including transcription, RNA splicing and protein translation.

  • There are a variety of classes of lncRNA, based on their structures and/or mechanisms of action, but their study has been limited by their low levels of expression and relatively poor conservation between species.

  • LncRNAs are crucial regulators of cell differentiation, development and disease; in the heart, their expression is often associated with stress conditions, and they participate in the pathophysiological remodelling associated with cardiac hypertrophy and heart failure.

  • Studies have shown that dysregulation of lncRNAs is associated with a variety of cardiac diseases, including coronary artery disease, myocardial infarction, heart failure and arrhythmias.

  • Indications from studies in animal models and humans reveal that lncRNAs have great potential as biomarkers for disease diagnosis and as novel targets for the treatment of cardiac disease.

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Fig. 1: lncRNA mechanisms of action.
Fig. 2: lncRNA regulation of cardiac hypertrophy induced by calcium and NFAT.
Fig. 3: lncRNA regulation of miRNA-dependent cardiac hypertrophy.
Fig. 4: lncRNA regulation of chromatin-mediated cardiac hypertrophy.

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Acknowledgements

D.-Z.W. is funded by National Institutes of Health R01HL168900, R01HL165794, R01HL149401, R01HL141853 and R01HL133216, and Additional Ventures, Single Ventricle Research Award #1014383.

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Authors and Affiliations

  1. Center for Regenerative Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA

    John D. Mably & Da-Zhi Wang

  2. USF Health Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA

    John D. Mably & Da-Zhi Wang

  3. Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA

    John D. Mably & Da-Zhi Wang

  4. Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA

    Da-Zhi Wang

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Mably, J.D., Wang, DZ. Long non-coding RNAs in cardiac hypertrophy and heart failure: functions, mechanisms and clinical prospects. Nat Rev Cardiol 21, 326–345 (2024). https://doi.org/10.1038/s41569-023-00952-5

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