Noncoding RNAs are fundamental regulators of gene expression. Both microRNAs and long noncoding RNAs have been shown to contribute widely to the initiation and development of cardiovascular diseases, including cardiac arrhythmias, atherosclerosis, fibrosis, heart failure, hypertrophy, and myocardial infarction, as summarized in this comprehensive collection of articles from Nature Reviews Cardiology. Identifying the mechanistic role of noncoding RNAs in the pathophysiology of these conditions might lead to their use as diagnostic or prognostic biomarkers, or even as targeted therapeutic agents.
Reviews
Noncoding RNAs and myocardial fibrosis
Thomas Thum
doi:10.1038/nrcardio.2014.125
Nature Reviews Cardiology 11, 655-663 (2014)
During stress or injury-induced cardiac remodelling, fibroblasts increase production of extracellular matrix proteins, which leads to fibrosis formation, and consequently, heart failure. In this Review, Thomas Thum describes the contribution of noncoding RNAs to this process, with a specific focus on microRNAs that might be used as future therapeutic targets or biomarkers for cardiac fibrosis.
MicroRNAs and atrial fibrillation: mechanisms and translational potential
Xiaobin Luo, Baofeng Yang & Stanley Nattel
doi:10.1038/nrcardio.2014.178
Nature Reviews Cardiology 12, 80-90 (2015)
Available treatments for atrial fibrillation (AF) often lack sufficient efficacy or have considerable complications, but novel therapies based on the underlying molecular mechanisms of AF can provide useful alternatives. MicroRNAs (miRNAs) regulate gene transcription, and constitute a promising therapeutic approach for the treatment of AF. In this Review article, Luo et al. provide a comprehensive overview of the mechanisms of miRNA action, and explore the available experimental evidence supporting a role for miRNAs as novel therapeutic targets for AF.
MicroRNAs in myocardial infarction
Reinier A. Boon & Stefanie Dimmeler
doi:10.1038/nrcardio.2014.207
Nature Reviews Cardiology 12, 135-142 (2015)
MicroRNAs regulate the processes that underlie cardiac remodelling after myocardial infarction, including angiogenesis and cardiomyocyte apoptosis and proliferation. In this Review, Boon and Dimmeler summarize the microRNAs that are involved with these postischaemic pathways, and discuss potential therapeutic interventions to enhance cardiac regeneration in patients with acute myocardial infarction.
MicroRNA-mediated mechanisms of the cellular stress response in atherosclerosis
Andreas Schober, Maliheh Nazari-Jahantigh & Christian Weber
doi:10.1038/nrcardio.2015.38
Nature Reviews Cardiology 12, 361-374 (2015)
The accumulation of lipid-laden macrophages in atherosclerotic lesions occurs preferentially at branching sites owing to poor adaptation of endothelial cells to disturbed blood flow. MicroRNAs (miRNAs) have been implicated in the pathogenic mechanisms of unresolved inflammation that precede and potentiate atherosclerosis. In this Review, Schober and colleagues provide an overview of the role of miRNAs in homeostasis and dysfunction of endothelial cells and macrophages in atherosclerosis, and explore the potential of novel miRNA-based diagnostics and therapeutic strategies.
Long noncoding RNAs in cardiac development and ageing
Yvan Devaux, Jennifer Zangrando, Blanche Schroen, Esther E. Creemers, Thierry Pedrazzini, Ching-Pin Chang, Gerald W. Dorn II, Thomas Thum, Stephane Heymans & for the Cardiolinc network
doi:10.1038/nrcardio.2015.55
Nature Reviews Cardiology 12, 415-425 (2015)
Long noncoding RNAs (lncRNAs) regulate cellular and tissue function by activating or repressing gene expression. In this Review, Devaux and colleagues summarize the mechanisms by which lncRNAs exert their epigenetic effects, and discuss their role in cardiac development and ageing, with emphasis on the importance of chromatin remodelling. The authors also discuss the potential of lncRNAs to be used as biomarkers and therapeutic agents.
Epigenetic modifications and noncoding RNAs in cardiac hypertrophy and failure
Carolina M. Greco & Gianluigi Condorelli
doi:10.1038/nrcardio.2015.71
Nature Reviews Cardiology 12, 488-497 (2015)
Cardiomyocyte function is regulated by epigenetic modifications (to cytosine residues on DNA, and post-translational acetylation or methylation of histones), as well as by noncoding RNAs (such as microRNAs and long noncoding RNAs). In this Review, Greco and Condorelli describe the complex roles of these two layers of gene-expression regulation in the pathogenesis of cardiac hypertrophy and failure.
MicroRNAs in platelet function and cardiovascular disease
David D. McManus & Jane E. Freedman
doi:10.1038/nrcardio.2015.101
Nature Reviews Cardiology, advance online publication, Published online 07 July 2015
Despite being anucleate, platelets contain RNA transcripts, including microRNAs, which are involved in regulating platelet function and which can also be transferred to other vascular cells. In this Review, McManus and Freedman summarize the mechanistic roles of platelet-derived miRNAs in acute atherogenic and thrombotic diseases, such as acute coronary syndromes and stroke. These miRNAs might also be used as biomarkers of cardiovascular disease susceptibility, prognosis, and treatment.
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