Dawid Miskowiec, Jaroslaw D. Kasprzak


Abstract: MicroRNAs (miRNAs) are a conserved class of small, 17-25 nucleotides long, noncoding RNAs. They act as controllers of gene expression patterns, either by blocking translation or inducing miRNA degradation by sequence-specific hybridization. Several miRNAs have been proposed as potential disease-specific biomarker in cardiovascular diseases. The diagnostic value of assessing circulating miRNAs levels has been evaluated in numerous studies, mainly regarding acute myocardial infarction. Initial promising results from preclinical studies suggest the potential for future miRNA-based therapies. In our review, we focus on the current developments showing the role of miRNAs in the acute myocardial infarction, emphasizing diagnostic utility of miRNAs as promising new biomarkers of AMI and their therapeutic potential.

Key words:microRNA, myocardial infarction, coronary artery disease, myocardium, gene expression regulation.


microRNA, myocardial infarction, coronary artery disease, myocardium, gene expression regulation.

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Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Nature. 2001; 409(6822): 860–921.

Wilusz JE, Sunwoo H, Spector DL. Long noncoding RNAs: functional surprises from the RNA world. Genes Dev. 2009;23(13):1494–504.

Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116(2): 281–97.

Jonas S, Izaurralde E. Towards a molecular understanding of microRNA-mediated gene silencing. Nat Rev Genet. 2015; 16(7): 421–33.

Du T, Zamore PD. microPrimer: the biogenesis and function of microRNA. Dev Camb Engl. 2005; 132(21): 4645–52.

Kozomara A, Griffiths-Jones S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res. 2011;39 (Database issue): D152–7.

Guo H, Ingolia NT, Weissman JS, Bartel DP. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010; 466(7308): 835–40.

Baek D, Villén J, Shin C, Camargo FD, Gygi SP, Bartel DP. The impact of microRNAs on protein output. Nature. 2008; 455(7209): 64–71.

Selbach M, Schwanhäusser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N. Widespread changes in protein synthesis induced by microRNAs. Nature. 2008; 455(7209): 58–63.

Liang Y, Ridzon D, Wong L, Chen C. Characterization of microRNA expression profiles in normal human tissues. BMC Genomics. 2007; 8:166.

Zhang J, Li S, Li L, et al. Exosome and Exosomal MicroRNA: Trafficking, Sorting, and Function. Genomics Proteomics Bioinformatics. 2015; 13(1): 17–24.

Miœkowiec D, Kasprzak JD. MicroRNAs as new biomarkers of the cardiovascular diseases - current communications review. Pol Przegl Kardiol. 2013; 15(1): 69–72.

Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007; 9(6): 654–9.

Lee Y, Ahn C, Han J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003; 425(6956): 415–9.

Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 2014; 15(8): 509–24.

Creemers EE, Tijsen AJ, Pinto YM. Circulating MicroRNAs Novel Biomarkers and Extracellular Communicators in Cardiovascular Disease? Circ Res. 2012; 110(3): 483–95.

Weber JA, Baxter DH, Zhang S, et al. The microRNA spectrum in 12 body fluids. Clin Chem. 2010; 56(11): 1733–41.

D’Alessandra Y, Devanna P, Limana F, et al. Circulating microRNAs are new and sensitive biomarkers of myocardial infarction. Eur Heart J. 2010; 31(22): 2765–73.

Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl AcadSci U S A. 2008; 105(30): 10513–8.

Turchinovich A, Weiz L, Langheinz A, Burwinkel B. Characterization of extracellular circulating microRNA. Nucleic Acids Res. 2011; 39(16): 7223–33.

Lee LW, Zhang S, Etheridge A, et al. Complexity of the microRNA repertoire revealed by next-generation sequencing. RNA. 2010; 16(11): 2170–80.

Wang Y, Zheng D, Tan Q, Wang MX, Gu L-Q. Nanopore-based detection of circulating microRNAs in lung cancer patients. Nat Nanotechnol. 2011; 6(10): 668–74.

Zhao Y, Zhou L, Tang Z. Cleavage-based signal amplification of RNA. Nat Commun. 2013; 4: 1493.

Fichtlscherer S, De Rosa S, Fox H, et al. Circulating microRNAs in patients with coronary artery disease. Circ Res. 2010; 107(5): 677–84.

Klimczak D, Paczek L, Jazdzewski K, Kuch M. MicroRNAs: powerful regulators and potential diagnostic tools in cardiovascular disease. Kardiol Pol. 2015; 73(1): 1–6.

Sayed ASM, Xia K, Yang T-L, Peng J. Circulating microRNAs: A Potential Role in Diagnosis and Prognosis of Acute Myocardial Infarction. Dis Markers. 2013; 35(5): 561–6.

Van Rooij E, Quiat D, Johnson BA, et al. A Family of microRNAs Encoded by Myosin Genes Governs Myosin Expression and Muscle Performance. Dev Cell. 2009; 17(5): 662–73.

Economou EK, Oikonomou E, Siasos G, et al. The role of microRNAs in coronary artery disease: From pathophysiology to diagnosis and treatment. Atherosclerosis. 2015; 241(2): 624–33.

Adachi T, Nakanishi M, Otsuka Y, et al. Plasma microRNA 499 as a biomarker of acute myocardial infarction. Clin Chem. 2010; 56(7): 1183–5.

Wang G-K, Zhu J-Q, Zhang J-T, et al. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. EurHeart J. 2010; 31(6): 659–66.

Bialek SG, Górko D, Zajkowska A, et al. Release kinetics of circulating miRNA-208a in early phase of myocardial infarction. Kardiol Pol [Internet]. 2015 [cited 2015 Jul 10]; Available from: http://ojs.kardiologiapolska.pl/kp/article/view/KP. a2015.0067

Zile MR, Mehurg SM, Arroyo JE, Stroud RE, DeSantis SM, Spinale FG. Relationship between the temporal profile of plasma microRNA and left ventricular remodeling in patients after myocardial infarction. Circ Cardiovasc Genet. 2011; 4(6): 614–9.

Corsten MF, Dennert R, Jochems S, et al. Circulating MicroRNA-208b and MicroRNA-499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genet. 2010; 3(6): 499–506.

Devaux Y, Vausort M, Goretti E, et al. Use of circulating microRNAs to diagnose acute myocardial infarction. Clin Chem. 2012; 58(3): 559–67.

Li C, Fang Z, Jiang T, et al. Serum microRNAs profile from genome-wide serves as a fingerprint for diagnosis of acute myocardial infarction and angina pectoris. BMC Med Genomics. 2013; 6:16.

Gidlöf O, Smith JG, Miyazu K, et al. Circulating cardio-enriched microRNAs are associated with long-term prognosis following myocardial infarction. BMC CardiovascDisord. 2013; 13(1): 12.

Devaux Y, Mueller M, Haaf P, et al. Diagnostic and prognostic value of circulating microRNAs in patients with acute chest pain. J Intern Med. 2015; 277(2): 260–71.

Endo K, Weng H, Naito Y, et al. Classification of various muscular tissues using miRNA profiling. Biomed Res Tokyo Jpn. 2013; 34(6): 289–99.

Widera C, Gupta SK, Lorenzen JM, et al. Diagnostic and prognostic impact of six circulating microRNAs in acute coronary syndrome. J Mol Cell Cardiol. 2011; 51(5): 872–5.

Cheng C, Wang Q, You W, Chen M, Xia J. MiRNAs as biomarkers of myocardial infarction: a meta-analysis. PloS One. 2014; 9(2): e88566.

Shieh JTC, Huang Y, Gilmore J, Srivastava D. Elevated miR-499 Levels Blunt the Cardiac Stress Response. PLoS ONE. 2011; 6(5): e19481.

Zhang L, Chen X, Su T, et al. Circulating miR-499 are novel and sensitive biomarker of acute myocardial infarction. J Thorac Dis. 2015; 7(3): 303–8.

Olivieri F, Antonicelli R, Lorenzi M, et al. Diagnostic potential of circulating miR-499-5p in elderly patients with acute non ST-elevation myocardial infarction. Int J Cardiol. 2013; 167(2): 531–6.

Yao Y, Du J, Cao X, et al. Plasma Levels of MicroRNA-499 Provide an Early Indication of Perioperative Myocardial Infarction in Coronary Artery Bypass Graft Patients. PLoS ONE [Internet]. 2014 Aug 11 [cited 2015 Jul 13]; 9(8). Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4128681/

Han M, Toli J, Abdellatif M. MicroRNAs in the cardiovascular system.CurrOpinCardiol. 2011; 26(3): 181–9.

Liu N, Bezprozvannaya S, Williams AH, et al. microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart. Genes Dev. 2008; 22(23): 3242–54.

Ai J, Zhang R, Li Y, et al. Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. BiochemBiophys Res Commun. 2010; 391(1): 73–7.

Mishima Y, Stahlhut C, Giraldez AJ. miR-1-2 gets to the heart of the matter. Cell. 2007; 129(2): 247–9.

Zhao Y, Ransom JF, Li A, et al. Dysregulation of Cardiogenesis, Cardiac Conduction, and Cell Cycle in Mice Lacking miRNA-1-2. Cell. 2007; 129(2): 303–17.

Yang B, Lin H, Xiao J, et al. The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat Med. 2007; 13(4): 486–91.

Thum T, Gross C, Fiedler J, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008; 456(7224): 980–4.

Rooij E van, Sutherland LB, Liu N, et al. A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc Natl Acad Sci. 2006; 103(48): 18255–60.

Long G, Wang F, Duan Q, et al. Human Circulating MicroRNA-1 and MicroRNA-126 as Potential Novel Indicators for Acute Myocardial Infarction. Int J Biol Sci. 2012; 8(6): 811–8.

Meder B, Keller A, Vogel B, et al. MicroRNA signatures in total peripheral blood as novel biomarkers for acute myocardial infarction. Basic Res Cardiol. 2011; 106(1): 13–23.

Vogel B, Keller A, Frese KS, et al. Refining diagnostic microRNA signatures by whole-miRNome kinetic analysis in acute myocardial infarction. Clin Chem. 2013; 59(2): 410–8.

Zhong J, He Y, Chen W, Shui X, Chen C, Lei W. Circulating microRNA-19a as a Potential Novel Biomarker for Diagnosis of Acute Myocardial Infarction. Int J Mol Sci. 2014; 15(11): 20355–64.

Van Rooij E, Marshall WS, Olson EN. Toward microRNA-based therapeutics for heart disease: the sense in antisense. Circ Res. 2008; 103(9): 919–28.

Van Rooij E, Sutherland LB, Thatcher JE, et al. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl AcadSci U S A. 2008; 105(35): 13027–32.

Sahoo S, Losordo DW. Exosomes and cardiac repair after myocardial infarction. Circ Res. 2014; 114(2): 333–44.

Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJA. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011; 29(4): 341–5.

Christianson HC, Svensson KJ, van Kuppevelt TH, Li J-P, Belting M. Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity. Proc Natl AcadSci U S A. 2013; 110(43): 17380–5.

Janssen HLA, Reesink HW, Lawitz EJ, et al. Treatment of HCV Infection by Targeting MicroRNA. N Engl J Med. 2013; 368(18): 1685–94.

Bader AG. miR-34 - a microRNA replacement therapy is headed to the clinic. Front Genet. 2012; 3:120.

Van Rooij E, Olson EN. MicroRNA therapeutics for cardiovascular disease: opportunities and obstacles. Nat RevDrugDiscov. 2012; 11(11): 860–72

DOI: http://dx.doi.org/10.24125/sanamed.v10i2.42


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