microRNAs in heart disease: putative novel therapeutic targets?

Condorelli, Gianluigi; Latronico, Michael V.G.; Dorn, Gerald W.

doi:10.1093/eurheartj/ehp573

Cited by 150 publications

(120 citation statements)

References 100 publications

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“…Although miR-based therapeutics such as antimiRs or miR mimics have not yet been approved for degenerative muscle diseases, targets exist (e.g., Condorelli et al 2010;Patrick et al 2010), and >20 candidate siRNA/ shRNA and miR therapeutics have been evaluated in clinical trials (Burnett and Rossi 2012). Moreover, the first anti-miR candidate therapeutic-miravirsen, a chemically modified oligonucleotide designed to inhibit miR-122-has advanced to a phase II trial (Santaris Pharma, NCT01200420) to treat chronic hepatitis C virus infection.…”

Section: Future Prospectsmentioning

confidence: 99%

BAF60 A, B, and Cs of muscle determination and renewal

Puri

Mercola

2012

Genes Dev.

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Developmental biologists have defined many of the diffusible and transcription factors that control muscle differentiation, yet we still have only rudimentary knowledge of the mechanisms that dictate whether a myogenic progenitor cell forms muscle versus alternate lineages, including those that can be pathological in a state of disease or degeneration. Clues about the molecular basis for lineage determination in muscle progenitors are only now emerging from studies of chromatin modifications that avail myogenic genes for transcription, together with analysis of the composition and activities of the chromatin-modifying complexes themselves. Here we review recent progress on muscle determination and explore a unifying theme that environmental cues from the stem or progenitor niche control the selection of specific subunit variants of the switch/sucrose nonfermentable (SWI/SNF) chromatin-modifying complex, creating a combinatorial code that dictates whether cells adopt myogenic versus nonmyogenic cell fates. A key component of the code appears to be the mutually exclusive usage of the a, b, and c variants of the 60-kD structural subunit BAF60 (BRG1/BRM-associated factor 60), of which BAF60c is essential to activate both skeletal and cardiac muscle programs. Since chromatin remodeling governs myogenic fate, the combinatorial assembly of the SWI/SNF complex might be targeted to develop drugs aimed at the therapeutic reduction of compensatory fibrosis and fatty deposition in chronic muscular disorders.

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Section: Future Prospectsmentioning

confidence: 99%

BAF60 A, B, and Cs of muscle determination and renewal

Puri

Mercola

2012

Genes Dev.

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“…However, the regulation and the function of TWF1 in heart disease are not clear. Recently, a new gene regulator, microRNA (miRNA), was reported to have an important role in heart disease (Chen et al, 2009;Condorelli et al, 2010;Wang et al, 2010), including cardiac hypertrophy. miRNAs are a class of conserved, single-stranded non-coding RNAs consisting of 18-25 nucleotides.…”

Section: Introductionmentioning

confidence: 99%

Attenuation of microRNA-1 derepresses the cytoskeleton regulatory protein twinfilin-1 to provoke cardiac hypertrophy

Song

Zou

et al. 2010

Journal of Cell Science

129

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MicroRNAs are involved in several aspects of cardiac hypertrophy, including cardiac growth, conduction, and fibrosis. However, their effects on the regulation of the cardiomyocyte cytoskeleton in this pathological process are not known. Here, with microRNA microarray and small RNA library sequencing, we show that microRNA-1 (miR-1) is the most abundant microRNA in the human heart. By applying bioinformatic target prediction, a cytoskeleton regulatory protein twinfilin-1 was identified as a potential target of miR-1. Overexpression of miR-1 not only reduced the luciferase activity of the reporter containing the 3′ untranslated region of twinfilin-1 mRNA, but also suppressed the endogenous protein expression of twinfilin-1, indicating that twinfilin-1 is a direct target of miR-1. miR-1 was substantially downregulated in the rat hypertrophic left ventricle and phenylephrine-induced hypertrophic cardiomyocytes, and accordingly, the protein level of twinfilin-1 was increased. Furthermore, overexpression of miR-1 in hypertrophic cardiomyocytes reduced the cell size and attenuated the expression of hypertrophic markers, whereas silencing of miR-1 in cardiomyocytes resulted in the hypertrophic phenotype. In accordance, twinfilin-1 overexpression promoted cardiomyocyte hypertrophy. Taken together, our results demonstrate that the cytoskeleton regulatory protein twinfilin-1 is a novel target of miR-1, and that reduction of miR-1 by hypertrophic stimuli induces the upregulation of twinfilin-1, which in turn evokes hypertrophy through the regulation of cardiac cytoskeleton.

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“…More than 700 human miRNAs have been identified and there seems to be 150 to 200 of them expressed in the heart 10 . This number is expected to grow even further, due to the recent development of sequencing technologies and computational prediction methods 19,20 .…”

Section: Micrornasmentioning

confidence: 99%

“…In humans, the role of this mechanism in hypertrophy remains to be clarified, as this species is not able to reverse the MHC isoforms, and the β-MHC is the predominant form, together with the miR-208b 31 . In addition, experimental models must be viewed with caution when extrapolating data, as they are artificial and may not accurately mimic the clinical conditions observed in humans 10 .…”

Section: Micrornas and Heart Failurementioning

confidence: 99%

“…Implicated in the regulation of gene expression during fetal development and in adult individuals 8,9 , many of these microRNAs increase or decrease in the heart in response to physiological stress, injury or hemodynamic overload 10 . The study of the behavior of these molecules in physical exercise therefore represents a great potential for new discoveries of this type of therapeutic modality in HF.…”

Section: Introductionmentioning

confidence: 99%

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Exercício físico e microRNAs: novas fronteiras na insuficiência cardíaca

Fernandes-Silva¹,

Carvalho²,

Guimarães³

et al. 2012

Arq. Bras. Cardiol.

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Although the impact of exercise on survival of patients with heart failure has been recently questioned, exercise training improves quality of life, functional capacity, inflammation, endothelial and autonomic function. In recent years, interest has increased regarding a group of small non-protein coding RNAs called microRNAs.Studies have shown that the expression of these molecules changes in several pathological conditions, such as myocardial infarction, myocardial ischemia and heart failure, and when clinical improvement occurs, they seem to normalize. With the potential for practical applicability, markers that may be useful in diagnostic and prognostic assessment of heart failure have been identified, such as miR-423-5p. In addition, results of experimental studies have indicated that there are potential therapeutic effects of microRNAs.MicroRNAs are involved in the regulation of gene expression during fetal development and in adult individuals, increasing or decreasing in the heart in response to physiological stress, injury or hemodynamic overload. Thus, the study of the behavior of these molecules in physical exercise has brought important information about the effects of this therapeutic modality and represents a new era in the understanding of heart failure.This review aims to integrate the evidence on microRNAs in heart failure with greater relevance in the study of physical exercise.

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microRNAs in heart disease: putative novel therapeutic targets?

Cited by 150 publications

References 100 publications

BAF60 A, B, and Cs of muscle determination and renewal

BAF60 A, B, and Cs of muscle determination and renewal

Attenuation of microRNA-1 derepresses the cytoskeleton regulatory protein twinfilin-1 to provoke cardiac hypertrophy

Exercício físico e microRNAs: novas fronteiras na insuficiência cardíaca

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