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Therapeutic Use of MicroRNAs in Myocardial Diseases

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Abstract

The discovery of regulatory non-coding (nc) RNAs has opened a new world in cell biology. Within this class of ncRNAs, microRNAs (miRNAs) have been found to be involved in many cellular functions. Regarding the cardiovascular system, miRNAs regulate cardiomyocyte size and survival, the action potential, angiogenesis, mitochondrial function, and energetics. Moreover, misexpression of miRNAs has been linked to pathology, and altered levels of certain miRNAs even may cause disease. Thus, the manipulation of miRNAs, by affecting the biological processes in which they are implicated, may be used to improve cardiac function. The expression of microRNAs can be modulated through different approaches. This article reviews these issues in relation to the therapeutic potential of miRNAs for heart failure.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Small EM, Olson EN. Pervasive roles of microRNAs in cardiovascular biology. Nature. 2011;469:336–42.

    Article  PubMed  CAS  Google Scholar 

  2. Fabian MR, Sonenberg N, Filipowicz W. Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem. 2010;79:351–79.

    Article  PubMed  CAS  Google Scholar 

  3. Condorelli G, Latronico MV, Dorn GW, 2nd. microRNAs in heart disease: putative novel therapeutic targets? Eur Heart J 2010.

  4. Bauersachs J. Regulation of myocardial fibrosis by MicroRNAs. J Cardiovasc Pharmacol. 2010;56:454–9.

    Article  PubMed  CAS  Google Scholar 

  5. Li P. MicroRNAs in cardiac apoptosis. J Cardiovasc Transl Res. 2010;3:219–24.

    Article  PubMed  Google Scholar 

  6. Latronico MV, Condorelli G. RNA silencing: small RNA-mediated posttranscriptional regulation of mRNA and the implications for heart electropathophysiology. J Cardiovasc Electrophysiol. 2009;20:230–7.

    Article  PubMed  Google Scholar 

  7. Bonauer A, Boon RA, Dimmeler S. Vascular microRNAs. Curr Drug Targets. 2010;11:943–9.

    Article  PubMed  CAS  Google Scholar 

  8. Latronico MV, Condorelli G. microRNAs in hypertrophy and heart failure. Exp Biol Med (Maywood). 2011;236:125–31.

    Article  CAS  Google Scholar 

  9. Davis S, Propp S, Freier SM, et al. Potent inhibition of microRNA in vivo without degradation. Nucleic Acids Res. 2009;37:70–7.

    Article  PubMed  CAS  Google Scholar 

  10. Krutzfeldt J, Rajewsky N, Braich R, et al. Silencing of microRNAs in vivo with 'antagomirs'. Nature. 2005;438:685–9.

    Article  PubMed  Google Scholar 

  11. Care A, Catalucci D, Felicetti F, et al. MicroRNA-133 controls cardiac hypertrophy. Nat Med. 2007;13:613–8.

    Article  PubMed  CAS  Google Scholar 

  12. da Costa Martins PA, Salic K, Gladka MM, et al. MicroRNA-199b targets the nuclear kinase Dyrk1a in an auto-amplification loop promoting calcineurin/NFAT signalling. Nat Cell Biol. 2010;12:1220–7.

    Article  PubMed  Google Scholar 

  13. Thum T, Gross C, Fiedler J, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008;456:980–4.

    Article  PubMed  CAS  Google Scholar 

  14. Esau C, Davis S, Murray SF, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab. 2006;3:87–98.

    Article  PubMed  CAS  Google Scholar 

  15. Kurreck J. Antisense technologies. Improvement through novel chemical modifications. Eur J Biochem. 2003;270:1628–44.

    Article  PubMed  CAS  Google Scholar 

  16. Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 2005;65:6029–33.

    Article  PubMed  CAS  Google Scholar 

  17. Elmen J, Lindow M, Silahtaroglu A, et al. Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver. Nucleic Acids Res. 2008;36:1153–62.

    Article  PubMed  CAS  Google Scholar 

  18. • Elmen J, Lindow M, Schutz S, et al. LNA-mediated microRNA silencing in non-human primates. Nature. 2008;452:896–9. This study demonstrated that effective and long-lasting downregulation of microRNAs also can be achieved in vivo in primates.

    Article  PubMed  CAS  Google Scholar 

  19. •• Lanford RE, Hildebrandt-Eriksen ES, Petri A, et al. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science. 2010;327:198–201. This study, showing that administration of an anti-microRNA antisense oligonucleotide markedly suppresses viremia in chimpanzees with infected with chronic hepatitis C, demonstrated the importance of miR-122 for the hepatitis C virus and that microRNAs can be targeted therapeutically in primates.

    Article  PubMed  CAS  Google Scholar 

  20. • Obad S, dos Santos CO, Petri A, et al. Silencing of microRNA families by seed-targeting tiny LNAs. Nat Genet. 2011;43:371–8. In this study, unconjugated tiny LNAs are shown to inhibit entire microRNA families in cultured cells and in a mouse breast-tumor model in vivo.

    Article  PubMed  CAS  Google Scholar 

  21. Patrick DM, Montgomery RL, Qi X, et al. Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice. J Clin Invest. 2010;120:3912–6.

    Article  PubMed  CAS  Google Scholar 

  22. Thum T, Chau N, Bhat B, et al. Comparison of different miR-21 inhibitor chemistries in a cardiac disease model. J Clin Invest. 2011;121:461–2. author reply 462–463.

    Article  PubMed  CAS  Google Scholar 

  23. Ebert MS, Neilson JR, Sharp PA. MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods. 2007;4:721–6.

    Article  PubMed  CAS  Google Scholar 

  24. Franco-Zorrilla JM, Valli A, Todesco M, et al. Target mimicry provides a new mechanism for regulation of microRNA activity. Nat Genet. 2007;39:1033–7.

    Article  PubMed  CAS  Google Scholar 

  25. Valastyan S, Reinhardt F, Benaich N, et al. A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell. 2009;137:1032–46.

    Article  PubMed  CAS  Google Scholar 

  26. • Lu Y, Xiao J, Lin H, et al. A single anti-microRNA antisense oligodeoxyribonucleotide (AMO) targeting multiple microRNAs offers an improved approach for microRNA interference. Nucleic Acids Res. 2009;37:e24. This study describes a “single-agent, multiple-targets” strategy to downregulate multiple microRNAs simultaneously.

    Article  PubMed  Google Scholar 

  27. Gregorevic P, Blankinship MJ, Allen JM, et al. Systemic delivery of genes to striated muscles using adeno-associated viral vectors. Nat Med. 2004;10:828–34.

    Article  PubMed  CAS  Google Scholar 

  28. Suckau L, Fechner H, Chemaly E, et al. Long-term cardiac-targeted RNA interference for the treatment of heart failure restores cardiac function and reduces pathological hypertrophy. Circulation. 2009;119:1241–52.

    Article  PubMed  CAS  Google Scholar 

  29. Wang K, Long B, Zhou J, et al. miR-9 and NFATc3 regulate myocardin in cardiac hypertrophy. J Biol Chem. 2010;285:11903–12.

    Article  PubMed  CAS  Google Scholar 

  30. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–54.

    Article  PubMed  CAS  Google Scholar 

  31. Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. 1993;75:855–62.

    Article  PubMed  CAS  Google Scholar 

  32. Marwick C. First "antisense" drug will treat CMV retinitis. JAMA. 1998;280:871.

    Article  PubMed  CAS  Google Scholar 

  33. Akdim F, Tribble DL, Flaim JD, et al. Efficacy of apolipoprotein B synthesis inhibition in subjects with mild-to-moderate hyperlipidaemia. Eur Heart J 2011, May 18 [Epub ahead of print].

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Acknowledgments

This work was supported by the Fondation LeDucq, Fondazione CARIPLO, the Italian Ministry of Health, and the Italian Ministry of Education, University and Research.

Disclosures

No potential conflicts of interest relevant to this article were reported.

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Authors and Affiliations

  1. Istituto di Ricovero e Cura a Carattere Scientifico Multimedica, Via Fantoli 16/15, Milan, 20138, Italy

    Michael V. G. Latronico

  2. National Research Council of Italy, Via Fantoli 16/15, Milan, 20138, Italy

    Gianlugi Condorelli

  3. Department of Medicine, University of California San Diego, La Jolla, CA, 92093-0613, USA

    Gianlugi Condorelli

Authors
  1. Michael V. G. Latronico
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  2. Gianlugi Condorelli
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Correspondence to Gianlugi Condorelli.

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Latronico, M.V.G., Condorelli, G. Therapeutic Use of MicroRNAs in Myocardial Diseases. Curr Heart Fail Rep 8, 193–197 (2011). https://doi.org/10.1007/s11897-011-0068-2

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  • DOI: https://doi.org/10.1007/s11897-011-0068-2

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