Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 3, March, p. 285–293

doi: 10.17219/acem/115088

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Relations between circulating and myocardial fibrosis-linked microRNAs with left ventricular reverse remodeling in dilated cardiomyopathy

Ewa Dziewięcka1,B,C,D, Justyna Totoń-Żurańska2,B,C, Paweł Wołkow2,B,C, Maria Kołton-Wróż2,B,C, Ewelina Pitera2,B,C, Sylwia Wiśniowska-Śmiałek1,B,C, Lusine Khachatryan3,B, Aleksandra Karabinowska3,B, Maria Szymonowicz3,B, Piotr Podolec1,E, Paweł Rubiś1,A,C,E,F

1 Department of Cardiac and Vascular Diseases, John Paul II Hospital, Kraków, Poland

2 Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Kraków, Poland

3 Jagiellonian University Medical College, Students’ Scientific Group at the Department of Cardiac and Vascular Diseases, John Paul II Hospital, Kraków, Poland

Abstract

Background. Left ventricular reverse remodeling (LVRR) determines clinical status and outcomes in dilated cardiomyopathy (DCM). The extent of myocardial fibrosis is connected to the systolic function of the heart. The recent discovery of the contribution of microRNAs (miRs) to the regulation of cardiac remodeling, LVRR and fibrosis warrants exploration.
Objectives. The aim of the study was to examine the predictive value of circulating and myocardial miR expression for LVRR in DCM.
Material and Methods. Seventy consecutive DCM patients (age 48 ±12.1 years, 90% male, ejection fraction (EF) 24.4% ±7.4%) were included in the study. At baseline, all patients underwent clinical assessment, echocardiography, venous blood sampling, and right ventricular endomyocardial biopsy. Circulating and myocardial miRs (miR-21, -26, -29, -30, -133a, and -423) were measured with quantitative real-time polymerase chain reaction (qRT-PCR). LVRR was defined as an increase in EF ≥ 10%, accompanied by a decrease in left ventricle end-diastolic diameter (LVEDd) ≥10% or LVEDd ≤ 33 mm/m2 between baseline and 3-month follow-up.
Results. At the 3-month follow-up, 4 patients had died and 3 patients had incomplete data. The remaining patients were divided according to the presence of LVRR into LVRR-present (n = 32, 51%) and LVRR-absent (n = 31, 49%) groups. Out of all the circulating and tissue miRs under study, only myocardial expression of miR-133a significantly differed between the LVRR-present and LVRR-absent group (1.22 (0.47–1.90) vs 0.61 (0.25–0.99) ΔCq, respectively, p < 0.01). miR-133a was found to be a significant LVRR predictor in unadjusted (odds ratio (OR) = 2.81 (1.23–6.40), p < 0.05) and adjusted for duration of disease, left ventricle end-diastolic (LVED) volume (LVEDvol), hs-troponin-T, and NT-proBNP (OR = 5.20 (1.13–24.050, p < 0.05) models.
Conclusion. From all of the circulating and tissue miRs, only myocardial miR-133a showed increased expression in LVRR-present patients and was found an independent LVRR predictor. This indicates a link between miR-133 and cardiac remodeling in DCM.

Key words

microRNA, dilated cardiomyopathy, left ventricle reverse remodeling

References (40)

  1. Ponikowski P, Voors AA, Anker SD, et al; ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016;18(8):891–975.
  2. Codd MB, Sugrue DD, Gersh BJ, Melton LJ. Epidemiology of idiopathic dilated and hypertrophic cardiomyopathy: A population-based study in Olmsted County, Minnesota, 1975–1984. Circulation. 1989;80(3):564–572.
  3. Elliott P, Andersson B, Arbustini E, et al. Classification of the cardiomyopathies: A position statement from the Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2008;29(2):270–276.
  4. Brooks A, Schinde V, Bateman AC, Gallagher PJ. Interstitial fibrosis in the dilated non-ischaemic myocardium. Heart. 2003;89(10):1255–1256.
  5. Merlo M, Pyxaras SA, Pinamonti B, Barbati G, Di Lenarda A, Sinagra G. Prevalence and prognostic significance of left ventricular reverse remodeling in dilated cardiomyopathy receiving tailored medical treatment. J Am Coll Cardiol. 2011;57(13):1468–1476.
  6. Rubiś P, Totoń-Zurańska J, Wiśniowska-Śmiałek S, et al. The relationship between myocardial fibrosis and myocardial microRNAs in dilated cardiomyopathy: A link between mir-133a and cardiovascular events. J Cell Mol Med. 2018;22(4):2514–2517.
  7. Small EM, Frost RJA, Olson EN. MicroRNAs add a new dimension to cardiovascular disease. Circulation. 2010;121(8):1022–1032.
  8. Wojciechowska A, Braniewska A, Kozar-Kamińska K. MicroRNA in cardiovascular biology and disease. Adv Clin Exp Med. 2017;26(5):865–874.
  9. Vegter EL, Meer P Van Der, Windt LJ De, Pinto YM, Voors AA. MicroRNAs in heart failure: From biomarker to target for therapy. Eur J Hear Fail. 2016;18(5):457–468.
  10. Rubiś P, Totoń-Żurańska J, Wiśniowska-Śmiałek S, et al. Relations between circulating microRNAs (miR-21, miR-26, miR-29, miR-30 and miR-133a), extracellular matrix fibrosis and serum markers of fibrosis in dilated cardiomyopathy. Int J Cardiol. 2017;231:201–206.
  11. Chyrchel B, Totoń-Żurańska J, Kruszelnicka O, et al. Association of plasma miR-223 and platelet reactivity in patients with coronary artery disease on dual antiplatelet therapy: A preliminary report. Platelets. 2015;26(6):593–597.
  12. Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc ­Imaging. 2015;16(3):233–271.
  13. Rubiś P, Wiśniowska-Śmiałek S, Biernacka-Fijałkowska B, et al. Left ventricular reverse remodeling is not related to biopsy-detected extracellular matrix fibrosis and serum markers of fibrosis in dilated cardiomyopathy, regardless of the definition used for LVRR. Heart Vessels. 2017;32(6):714–725.
  14. Pinto YM, Elliott PM, Arbustini E, et al. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: A position statement of the ESC working group on myocardial and pericardial diseases. Eur Heart J. 2016;37(23):1850–1858.
  15. Amorim S, Campelo M, Martins E, et al. Prevalence, predictors and prognosis of ventricular reverse remodeling in idiopathic dilated cardiomyopathy. Rev Port Cardiol. 2016;35(5):253–260.
  16. Ikeda Y, Inomata T, Fujita T, et al. Cardiac fibrosis detected by magnetic resonance imaging on predicting time course diversity of left ventricular reverse remodeling in patients with idiopathic dilated cardiomyopathy. Heart Vessels. 2016;31(11):1–10.
  17. Choi J-O, Kim EY, Lee GY, et al. Predictors of left ventricular reverse remodeling and subsequent outcome in nonischemic dilated cardiomyopathy. Circ J. 2013;77(2):462–469.
  18. Yu B, Li W, Al F, Chen Z. MicroRNA-33a deficiency inhibits proliferation and fibrosis through inactivation of TGF-β/Smad pathway in human cardiac fibroblasts. Pharmazie. 2017;72(8):456–460.
  19. Liu X, Wang L, Li H, et al. Coactivator-associated arginine methyltransferase 1 targeted by miR-15a regulates inflammation in acute coronary syndrome. Atherosclerosis. 2014;233(2):349–356.
  20. Kuosmanen SM, Hartikainen J, Hippeläinen M, Kokki H, Levonen A-L, Tavi P. MicroRNA profiling of pericardial fluid samples from patients with heart failure. PLoS One. 2015;10(3):e0119646.
  21. Li Q, Xie J, Li R, et al. Overexpression of microRNA-99a attenuates heart remodelling and improves cardiac performance after myocardial infarction. J Cell Mol Med. 2014;18(5):919–928.
  22. Devaux Y, Vausort M, McCann GP, et al. A panel of 4 microRNAs facilitates the prediction of left ventricular contractility after acute myocardial infarction. PLoS One. 2013;8(8):e70644.
  23. Satoh M, Minami Y, Takahashi Y, Tabuchi T, Nakamura M. Expression of microRNA-208 is associated with adverse clinical outcomes in human dilated cardiomyopathy. J Card Fail. 2010;16(5):404–410.
  24. Sucharov CC, Kao DP, Port JD, et al. Myocardial microRNAs associated with reverse remodeling in human heart failure. JCI Insight. 2017;2(2):1–16.
  25. Shah R, Ziegler O, Yeri A, et al. MicroRNAs associated with reverse left ventricular remodeling in humans identify pathways of heart failure progression. Circ Heart Fail. 2018;11(2):e004278.
  26. Szczerba E, Zajkowska A, Bochowicz A, et al. Rise in antifibrotic and decrease in profibrotic microRNA protect the heart against fibrosis during pregnancy: A preliminary study. Adv Clin Exp Med. 2018;27(7):867–872.
  27. Sucharov C, Bristow MR, Port JD. miRNA expression in the failing human heart: Functional correlates. J Mol Cell Cardiol. 2008;45(2):185–192.
  28. Thum T, Galuppo P, Wolf C, et al. MicroRNAs in the human heart: A clue to fetal gene reprogramming in heart failure. Circulation. 2007;116(3):258–267.
  29. Sayed D, Hong C, Chen IY, Lypowy J, Abdellatif M. MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ Res. 2007;100(3):416–424.
  30. Ivey KN, Muth A, Arnold J, et al. MicroRNA regulation of cell lineages in mouse and human embryonic stem cells. Cell Stem Cell. 2008;6(23):219–229.
  31. Carè A, Catalucci D, Felicetti F, et al. MicroRNA-133 controls cardiac hypertrophy. Nat Med. 2007;13(5):613–618.
  32. Besler C, Urban D, Watzka S, et al. Endomyocardial miR-133a levels correlate with myocardial inflammation, improved left ventricular function, and clinical outcome in patients with inflammatory cardiomyopathy. Eur J Heart Fail. 2016;18(12):1442–1451.
  33. Castaldi A, Zaglia T, Di Mauro V, et al. MicroRNA-133 modulates the β1-adrenergic receptor transduction cascade. Circ Res. 2014;115(2):273–283.
  34. He B, Xiao J, Ren A-J, et al. Role of miR-1 and miR-133a in myocardial ischemic postconditioning. J Biomed Sci. 2011;18(1):22.
  35. Saxena A, Tabin CJ. miRNA-processing enzyme Dicer is necessary for cardiac outflow tract alignment and chamber septation. Proc Natl Acad Sci U S A. 2010;107(1):87–91.
  36. Wang F, Long G, Zhao C, et al. Plasma microRNA-133a is a new marker for both acute myocardial infarction and underlying coronary artery stenosis. J Transl Med. 2013;11:222.
  37. 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):872–875.
  38. Gacoń J, Kabłak-Ziembicka A, Stępień E, et al. Decyzyjne mikroRNA (miR-124, -133a/b, -34a i -134) u pacjentów z zamkniętym naczyniem odpowiedzialnym za zawał z ostrym zespołem wieńcowym. Kardiol Pol. 2016;74(3):280–288.
  39. Eitel I, Adams V, Dieterich P, et al. Relation of circulating microRNA-133a concentrations with myocardial damage and clinical prognosis in ST-elevation myocardial infarction. Am Heart J. 2012;164(5):706–714.
  40. Keller T, Boeckel JN, Groß S, et al. Improved risk stratification in prevention by use of a panel of selected circulating microRNAs. Sci Rep. 2017;7(1):4511.