MicroRNAs in Cardiovascular Development and Diseases

Abstract

Small molecule microribonucleic acids (miRNAs) are coming up with a huge impact on the scientific world of therapeutics and diagnostics. These 22–24 nucleotide small noncoding RNAs acting as negative gene regulators are found to be involved in a broad range of homeostasis process. One of the major health‐related concerns in current scenario is the development of heart problems leading to cardiomyopathy and heart failure in extreme conditions. The disease condition is associated with both lifestyle and genetic factors. The role of miRNAs governing the regulation of the genes involved in heart development and diseases is being studied extensively. Some of the miRNAs present abundantly in heart and regulating the process of cardiovascular development and diseases are miR‐1, miR‐133, miR‐499, miR‐208 and miR‐199b. This article presents a brief review on the roles of these miRNAs in cardiac development and diseases along with their potential in heart regeneration.

Key Concepts

  • A large fraction of miRNAs are expressed in heart regulating the gene expression.
  • miR‐1/133b, miR‐208/499 and miR‐17‐92 clusters are majorly involved in the cardiovascular systems.
  • An imbalance or downregulation of the crucial miRNAs is associated with the development of cardiac diseases.
  • Heart regeneration can be achieved by the exogenous supply of deregulated miRNAs.

Keywords: mircoRNAs; cardiovascular development; cardiomyopathy; myocardial infarction; heart regeneration

Figure 1. Biogenesis and mechanism of action of microRNAs. Reproduced and adapted from Shruti et al. (2011) © Elsevier.
Figure 2. Involvement of miRNAs in heart development.
Figure 3. miRNAs involvement in heart failure and heart diseases.
close

References

Ashley MF and Qian L (2014) MiRiad roles for MicroRNAs in cardiac development and regeneration. Cells 3: 724–750.

Bonauer A, Carmona G, M I, et al. (2009) MicroRNA‐92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science 324 (5935): 1710–1713.

Chen JF, Mandel EM, Thomson JM, et al. (2006) The role of microRNA‐1 and microRNA‐133 in skeletal muscle proliferation and differentiation. Nature Genetics 38 (2): 228–233.

Chen J and Wang D‐Z (2012) microRNAs in cardiovascular development. Journal of Molecular and Cellular Cardiology 52 (5): 949–957.

Danielson LS, Park DS, Rotllan N, et al. (2013) Cardiovascular dysregulation of miR‐17‐92 causes a lethal hypertrophic cardiomyopathy and arrhythmogenesis. Journal of Federation of American Societies for Experimental Biology 27 (4): 1460–1467.

Darukeshwara J, Rajarajan AT, Sahana SB and Prasanna K (2014) Small engine, big power: MicroRNAs as regulators of cardiac diseases and regeneration. International Journal of Molecular Science 15 (9): 15891–15911.

Eric MS, Robert JAF and Eric NO (2010) MicroRNAs add a new dimension to cardiovascular disease. Circulation 121: 1022–1032.

Espinoza LRA and Wang DZ (2012) MicroRNAs in heart development. Current Topics in Developmental Biology 100: 279–317.

Eulalio A, Mano M, Dal FM, et al. (2012) Functional screening identifies miRNAs inducing cardiac regeneration. Nature 492 (7429): 376–381.

Gregory RI, Yan KP, Amuthan G, et al. (2004) The microprocessor complex mediates the genesis of microRNAs. Nature 432 (7014): 235–240.

Hynes CJ, Clancy JL and Preiss T (2012) miRNAs in cardiac disease: Sitting duck or moving target? IUBMB Life 64 (11): 872–878.

Jayawardena TM, Egemnazarov B, Finch EA, et al. (2012) MicroRNA‐mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circulation Research 110 (11): 1465–1473.

Joseph TCS, Yu H, Jacqueline G and Deepak S (2011) Elevated miR‐499 levels blunt the cardiac stress response. PLoS One 6 (5): e19481.

Katharina W, Johannes B, Angela B, et al. (2013) miR‐1/133a clusters cooperatively specify the cardiomyogenic lineage by adjustment of myocardin levels during embryonic heart development. PLoS Genetics 9 (9): e1003793.

Kimberly RC and Deepak S (2009) MicroRNA regulation of cardiovascular development. Circulation Research 104 (6): 724–732.

Krutzfeldt J, Rajewsky N, Braich R, et al. (2005) Silencing of microRNAs in vivo with ‘antagomirs’. Nature 438 (7068): 685–689.

Lee Y, Ahn C, Han J, et al. (2003) The nuclear RNase III Drosha initiates microRNA processing. Nature 425 (6956): 415–419.

Li X, Jiaji W, Zhuqing J, et al. (2013) MiR‐499 regulates cell proliferation and apoptosis during late‐stage cardiac differentiation via Sox6 and Cyclin D1. PLoS One 8 (9): e74504.

Marin M, Christian YQ, Chen C (2010) MicroRNAs and human disease. eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net. doi:10.1002/9780470015902.a0021433.

Mendell JT and Olson EN (2012) MicroRNAs in stress signaling and human disease. Cell 148 (6): 1172–1187.

Mishra PJ, Humeniuk R (2013) MicroRNA Polymorphisms. John Wiley & Sons Ltd, Chichester. http://www.els.net. doi:10.1002/9780470015902.a0022428.

Narry KV (2005) MicroRNA biogenesis: coordinated cropping and dicing. Nature Reviews Molecular Cell Biology 6: 376–385.

Neppl RL, Wang DZ (2010) MicroRNAs in Cardiovascular Disease. John Wiley & Sons Ltd, Chichester. http://www.els.net. doi:10.1002/9780470015902.a0022431.

Orom UA, Kauppinen S and Lund AH (2006) LNA–modified oligonucleotides mediate specific inhibition of microRNA function. Gene 372 (10): 137–141.

Poliseno L, Tuccoli A, Mariani L, et al. (2006) MicroRNAs modulate the angiogenic properties of HUVECs. Blood 108 (9): 3068–3071.

Porrello ER (2013) microRNAs in cardiac development and regeneration. Clinical Sciences (London) 125 (4): 151–166.

Qin DN, Qian L and Hu DL (2013) Effects of miR‐19b overexpression on proliferation, differentiation, apoptosis and Wnt/β‐catenin signaling pathway in P19 cell model of cardiac differentiation in vitro. Cell Biochemistry and Biophysics 66 (3): 709–722.

Rooij EV, Daniel Q, Brett AJ, et al. (2009) A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance. Developmental Cell 17 (5): 662–673.

Shruti K, Shrey K and Vibha R (2011) Micro RNAs: tiny sequences with enormous potential. Biochemical and Biophysical Research Communications 407 (3): 445–449.

Shyu AB, Wilkinson MF and van Hoof A (2008) Messenger RNA regulation: to translate or to degrade. EMBO Journal 27 (3): 471–481.

Staton AA, Giraldez AJ (2008) MicroRNAs in Development and Disease. John Wiley & Sons Ltd, Chichester. http://www.els.net. doi:10.1002/9780470015902.a0020863.

Suarez Y, Fernandez‐Hernando C, Pober JS and Sessa WC (2007) Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circulation Research 100 (8): 1164–1173.

Wang ZZ, Liao X and Zhang T (2009) Role of MicroRNAs in cardiac hypertrophy and heart failure. IUBMB Life 61 (6): 566–571.

Wang J, Stephanie BG, Margarita BC, et al. (2010) Bmp‐signaling regulates myocardial differentiation from cardiac progenitors through a micro RNA‐mediated mechanism. Developmental Cell 19 (6): 903–912.

William WD, Xianmin L, Li T, et al. (2014) Expression of microRNA miR‐17‐3p inhibits mouse cardiac fibroblast senescence by targeting Par4. Journal of Cell Science 128 (2): 293–304.

Zhang Y, Lv Q (2009) Comparative analysis of miRNA mediated gene regulation in mammals. John Wiley & Sons Ltd, Chichester. http://www.els.net. doi:10.1002/9780470015902.a0021754.

Further Reading

Annalisa C, Maria TC, Roberto G and Luigi MB (2013) Potential therapeutic role of microRNAs in ischemic heart disease. Journal of Cardiology 61 (5): 315–320.

Choi WY and Poss KD (2012) Cardiac regeneration. Current Topics on Developmental Biology 100: 319–344.

Devaux Y, Stammet P and Friberg H (2015) MicroRNAs: new biomarkers and therapeutic targets after cardiac arrest? Critical Care 19 (1): 54.

Flemming A (2014) Targetting miRNA pathology in heart disease. Nature Reviews in Drug Discovery 13: 336.

Gommans WM and Berezikov E (2012) Controlling miRNA regulation in disease. Methods Molecular Biology 822: 1–18.

Martins PADC and Windt LJD (2012) MicroRNAs in control of cardiac hypertrophy. Cardiovascular Research 93 (4): 563–572.

Thomas T, Daniele C and Johann B (2008) MicroRNAs: novel regulators in cardiac development and disease. Cardiovascular Research 79: 562–570.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Mishra, Shivangi, Yadav, Tanuja, Rani, Anshu, and Rani, Vibha(Jul 2015) MicroRNAs in Cardiovascular Development and Diseases. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021436]