Vol 25, No 6 (2018)
Original articles — Basic science and experimental cardiology
Published online: 2017-08-24

open access

Page views 3406
Article views/downloads 1437
Get Citation

Connect on Social Media

Connect on Social Media

Right ventricular morphology and function is not related with microRNAs and fibrosis markers in dilated cardiomyopathy

Paweł Rubiś, Justyna Totoń-Żurańska, Sylwia Wiśniowska-Śmiałek, Maria Kołton-Wróż, Paweł Wołkow, Ewa Wypasek, Lucyna Rudnicka-Sosin, Agnieszka Pawlak, Kozanecki Kozanecki, Lidia Tomkiewicz-Pająk, Piotr Podolec
Pubmed: 28840590
Cardiol J 2018;25(6):722-731.

Abstract

Background: The relationship between right ventricle (RV), extracellular matrix (ECM) fibrosis and fibrosis-linked, circulating microRNAs in dilated cardiomyopathy (DCM) is unknown.

Aim: The aim of the study was to uncover the associations between serum markers of ECM metabolism and circulating microRNAs with RV morphological and functional parameters.

Methods: The study population consisted of 70 consecutive DCM patients (ejection fraction 24.4 ± ± 7.4%). Based on detailed echocardiographic assessment — 15 patients had normal RV, whereas 55 patients had RV dilatation (RVD) and/or RV systolic dysfunction (RVSD). Procollagens type I and III carboxy- and amino-terminal peptides, osteopontin (OPN), TGF1-b1, connective tissue growth factor (CTGF), MMP-2, MMP-9 and TIMP-1 were measured in serum as well as expression of miR-21, miR-26, miR-29, miR-30 and miR-133a. All patients underwent endomyocardial biopsy.

Results: Biopsy-proven fibrosis was evenly distributed in two groups. Serum levels of fibrosis markers did not differ between groups. OPN, CTGF, MMP-2, and TIMP-1 correlated with RV parameters. Only miR-133 a was differently expressed in both groups. MiR-21, miR-26, miR-30, and miR-133a cor­related with RV morphological but without functional parameters. Not a single marker of fibrosis was independently associated with RV. MiR-30 was associated with RV impairment in the logistic regression model adjusted for age, sex, body mass index, and disease duration; however, lost its significance in the more comprehensive model.

Conclusions: Right ventricle structural and functional abnormalities are common in DCM. ECM fibrosis and serum markers are not associated with RV impairment. The prognostic value of studied microRNAs on RV is limited in DCM.

Article available in PDF format

View PDF Download PDF file

References

  1. Elliott P, Andersson B, Arbustini E, et al. Classification of the cardiomyopathies: a position statement from the european society of cardiology working group on myocardial and pericardial diseases. Eur Heart J. 2007; 29(2): 270–276.
  2. Mahmud M, Champion HC. Right ventricular failure complicating heart failure: pathophysiology, significance, and management strategies. Curr Cardiol Rep. 2007; 9(3): 200–208.
  3. 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. J Am Soc Echocardiogr. 2015; 28(1): 1–39.e14.
  4. Sackner-Bernstein JD, Sackner-Bernstein JD. The myocardial matrix and the development and progression of ventricular remodeling. Curr Cardiol Rep. 2000; 2(2): 112–119.
  5. Zhang Y, Tang W, Peng L, et al. Identification and validation of microRNAs as endogenous controls for quantitative polymerase chain reaction in plasma for stable coronary artery disease. Cardiol J. 2016; 23(6): 694–703.
  6. Vegter EL, van der Meer P, de Windt LJ, et al. MicroRNAs in heart failure: from biomarker to target for therapy. Eur J Heart Fail. 2016; 18(5): 457–468.
  7. 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.
  8. Majos E, Dąbrowski R, Szwed H. The right ventricle in patients with chronic heart failure and atrial fibrillation. Cardiol J. 2013; 20(3): 220–226.
  9. Reddy S, Bernstein D. Molecular Mechanisms of Right Ventricular Failure. Circulation. 2015; 132(18): 1734–1742.
  10. Henry WL, Gardin JM, Ware JH. Echocardiographic measurements in normal subjects from infancy to old age. Circulation. 1980; 62(5): 1054–1061.
  11. Cooper LT, Baughman KL, Feldman AM, et al. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Circulation. 2007; 116(19): 2216–2233.
  12. Brooks A, Schinde V, Bateman AC, et al. Interstitial fibrosis in the dilated non-ischaemic myocardium. Heart. 2003; 89(10): 1255–1256.
  13. 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.
  14. Rubiś P, Wiśniowska-Śmialek S, Wypasek E, et al. Fibrosis of extracellular matrix is related to the duration of the disease but is unrelated to the dynamics of collagen metabolism in dilated cardiomyopathy. Inflamm Res. 2016; 65(12): 941–949.
  15. Rouet-Benzineb P, Buhler JM, Dreyfus P, et al. Altered balance between matrix gelatinases (MMP-2 and MMP-9) and their tissue inhibitors in human dilated cardiomyopathy: potential role of MMP-9 in myosin-heavy chain degradation. Eur J Heart Fail. 1999; 1(4): 337–352.
  16. Herpel E, Singer S, Flechtenmacher C, et al. Extracellular matrix proteins and matrix metalloproteinases differ between various right and left ventricular sites in end-stage cardiomyopathies. Virchows Arch. 2005; 446(4): 369–378.
  17. Tyagi SC, Campbell SE, Reddy HK, et al. Matrix metalloproteinase activity expression in infarcted, noninfarcted and dilated cardiomyopathic human hearts. Mol Cell Biochem. 1996; 155(1): 13–21.
  18. Küçüker SA, Stetson SJ, Becker KA, et al. Evidence of improved right ventricular structure after LVAD support in patients with end-stage cardiomyopathy. J Heart Lung Transplant. 2004; 23(1): 28–35.
  19. Kakimoto Yu, Tanaka M, Kamiguchi H, et al. MicroRNA deep sequencing reveals chamber-specific miR-208 family expression patterns in the human heart. Int J Cardiol. 2016; 211: 43–48.
  20. Zhang Y, Wang X, Xu X, et al. Distinct microRNA expression signatures in human right atrial and ventricular myocardium. Mol Cell Biochem. 2012; 371(1-2): 23–29.
  21. De Rosa S, Fichtlscherer S, Lehmann R, et al. Transcoronary concentration gradients of circulating microRNAs. Circulation. 2011; 124(18): 1936–1944.
  22. Melman YF, Shah R, Danielson K, et al. Circulating microRMA-30d is associated with response to cardiac resynchronization therapy in heart failure and regulates cardiomyocyte apoptosis: a translational pilot study. Circulation. 2015; 131(25): 2202–2216.
  23. Li D, Ji L, Liu L, et al. Characterization of circulating microRNA expression in patients with a ventricular septal defect. PLoS One. 2014; 9(8): e106318.
  24. Sucharov CC, Sucharov J, Karimpour-Fard A, et al. Micro-RNA expression in hypoplastic left heart syndrome. J Card Fail. 2015; 21(1): 83–88.
  25. Lai CTM, Ng EKO, Chow Pc, et al. Circulating microRNA expression profile and systemic right ventricular function in adults after atrial switch operation for complete transposition of the great arteries. BMC Cardiovasc Disord. 2013; 13: 73.
  26. Tutarel O, Dangwal S, Bretthauer J, et al. Circulating miR-423_5p fails as a biomarker for systemic ventricular function in adults after atrial repair for transposition of the great arteries. Int J Cardiol. 2013; 167(1): 63–66.
  27. Satoh M, Minami Y, Takahashi Y, et al. Expression of microRNA-208 is associated with adverse clinical outcomes in human dilated cardiomyopathy. J Card Fail. 2010; 16(5): 404–410.
  28. 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.
  29. Wang H, Chen F, Tong J, et al. Circulating microRNAs as novel biomarkers for dilated cardiomyopathy. Cardiol J. 2017; 24(1): 65–73.