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Kinetics of selected serum markers of fibrosis in patients with dilated cardiomyopathy and different grades of diastolic dysfunction of the left ventricle

Sylwia Wiśniowska-Śmiałek, Ewa Dziewięcka, Katarzyna Holcman, Ewa Wypasek, Lusine Khachatryan, Aleksandra Karabinowska, Maria Szymonowicz, Agata Leśniak-Sobelga, Marta Hlawaty, Magdalena Kostkiewicz, Piotr Podolec, Paweł Rubiś
DOI: 10.5603/CJ.a2018.0143
·
Pubmed: 30484268

open access

Ahead of print
Original articles
Published online: 2018-11-26

Abstract

Background: Fibrosis of the extracellular matrix (ECM) in dilated cardiomyopathy (DCM) is common and compromises both systolic and diastolic function. The aim of this study was to investigate the kinetics of ECM fibrosis markers over a 12 month follow-up in patients with DCM based on the severity of diastolic dysfunction (DD).

Methods: Seventy consecutive DCM patients (48 ± 12.1 years, ejection fraction 24.4 ± 7.4%) were included in the study. The grade of DD was determined using the ASE/EACVI algorithm. Markers of ECM fibrosis were measured at baseline and at 3 and 12 month  follow-ups: collagen type I and III (PICP, PINP, PIIICP, PIIINP), tumor growth factor beta-1 (TGF1-β), connective tissue growth factor (CTGF) and galectin-3 were measured.

Results: Patients were divided into three groups according to DD severity: 30 patients with grade I, 18 with grade II and 22 with grade III of DD. Levels of PICP, PINP were increased over a 12-month period, while PIIINP decreased and PIIICP unchanged. Levels of TGF1-β decreased from the 3 to the 12-month points in grade I and II DD, and in grade III they remained unchanged. Levels of CTGF decreased over 12 months in grade III DD but were unchanged in grades I and II. Galectin-3 levels remained the same over all observation periods, irrespective of DD grade.

Conclusions: Regardless of the DD grade, markers of collagen type I synthesis increased, markers of collagen type III decreased. Levels of TGF and CTGF had a tendency to decrease. Galectin-3 was revealed not to be a marker discriminating the severity of DD.

Abstract

Background: Fibrosis of the extracellular matrix (ECM) in dilated cardiomyopathy (DCM) is common and compromises both systolic and diastolic function. The aim of this study was to investigate the kinetics of ECM fibrosis markers over a 12 month follow-up in patients with DCM based on the severity of diastolic dysfunction (DD).

Methods: Seventy consecutive DCM patients (48 ± 12.1 years, ejection fraction 24.4 ± 7.4%) were included in the study. The grade of DD was determined using the ASE/EACVI algorithm. Markers of ECM fibrosis were measured at baseline and at 3 and 12 month  follow-ups: collagen type I and III (PICP, PINP, PIIICP, PIIINP), tumor growth factor beta-1 (TGF1-β), connective tissue growth factor (CTGF) and galectin-3 were measured.

Results: Patients were divided into three groups according to DD severity: 30 patients with grade I, 18 with grade II and 22 with grade III of DD. Levels of PICP, PINP were increased over a 12-month period, while PIIINP decreased and PIIICP unchanged. Levels of TGF1-β decreased from the 3 to the 12-month points in grade I and II DD, and in grade III they remained unchanged. Levels of CTGF decreased over 12 months in grade III DD but were unchanged in grades I and II. Galectin-3 levels remained the same over all observation periods, irrespective of DD grade.

Conclusions: Regardless of the DD grade, markers of collagen type I synthesis increased, markers of collagen type III decreased. Levels of TGF and CTGF had a tendency to decrease. Galectin-3 was revealed not to be a marker discriminating the severity of DD.

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Keywords

dilated cardiomyopathy, diastolic dysfunction, markers of fibrosis

About this article
Title

Kinetics of selected serum markers of fibrosis in patients with dilated cardiomyopathy and different grades of diastolic dysfunction of the left ventricle

Journal

Cardiology Journal

Issue

Ahead of print

Article type

Original Article

Published online

2018-11-26

DOI

10.5603/CJ.a2018.0143

Pubmed

30484268

Keywords

dilated cardiomyopathy
diastolic dysfunction
markers of fibrosis

Authors

Sylwia Wiśniowska-Śmiałek
Ewa Dziewięcka
Katarzyna Holcman
Ewa Wypasek
Lusine Khachatryan
Aleksandra Karabinowska
Maria Szymonowicz
Agata Leśniak-Sobelga
Marta Hlawaty
Magdalena Kostkiewicz
Piotr Podolec
Paweł Rubiś

References (29)
  1. Ponikowski P, Voorse AA, Anker SD, et al. 2016 Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur J Heart Fail. 2016; 18: 891–975.
  2. Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016; 29(4): 277–314.
  3. Rubiś P, Totoń-Żurańska J, Wiśniowska-Śmiałek S, et al. Right ventricular morphology and function is not related with microRNAs and fibrosis markers in dilated cardiomyopathy. Cardiol J. 2017 [Epub ahead of print].
  4. Querejeta R, López B, González A, et al. Increased collagen type I synthesis in patients with heart failure of hypertensive origin: relation to myocardial fibrosis. Circulation. 2004; 110(10): 1263–1268.
  5. Klappacher G, Franzen P, Haab D, et al. Measuring extracellular matrix turnover in the serum of patients with idiopathic or ischemic dilated cardiomyopathy and impact on diagnosis and prognosis. Am J Cardiol. 1995; 75(14): 913–918.
  6. Dobaczewski M, Chen W, Frangogiannis NG. Transforming growth factor (TGF)-β signaling in cardiac remodeling. J Mol Cell Cardiol. 2011; 51(4): 600–606.
  7. Rubiś P, Wiśniowska-Smiałek S, Wypasek E, et al. 12-month patterns of serum markers of collagen synthesis, transforming growth factor and connective tissue growth factor are similar in new-onset and chronic dilated cardiomyopathy in patients both with and without cardiac fibrosis. Cytokine. 2017; 96: 217–227.
  8. Lang R, Badano L, 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.
  9. 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.
  10. Marijianowski MM, Teeling P, Mann J, et al. Dilated cardiomyopathy is associated with an increase in the type I/type III collagen ratio: a quantitative assessment. J Am Coll Cardiol. 1995; 25(6): 1263–1272.
  11. Pauschinger M, Knopf D, Petschauer S, et al. Dilated cardiomyopathy is associated with significant changes in collagen type I/III ratio. Circulation. 1999; 99(21): 2750–2756.
  12. Izawa H, Murohara T, Nagata K, et al. Mineralocorticoid receptor antagonism ameliorates left ventricular diastolic dysfunction and myocardial fibrosis in mildly symptomatic patients with idiopathic dilated cardiomyopathy: a pilot study. Circulation. 2005; 112(19): 2940–2945.
  13. Demir M, Acartürk E, Inal T, et al. Procollagen type I carboxy-terminal peptide shows left ventricular hypertrophy and diastolic dysfunction in hypertensive patients. Cardiovasc Pathol. 2007; 16(2): 69–74.
  14. Ihm SH, Youn HJ, Shin DI, et al. Serum carboxy-terminal propeptide of type I procollagen (PIP) is a marker of diastolic dysfunction in patients with early type 2 diabetes mellitus. Int J Cardiol. 2007; 122(3): e36–e38.
  15. Roongsritong C, Bradley J, Sutthiwan P, et al. Elevated carboxy-terminal peptide of procollagen type I in elderly patients with diastolic dysfunction. Am J Med Sci. 2006; 331(3): 131–133.
  16. Roongsritong C, Sadhu A, Pierce M, et al. Plasma carboxy-terminal peptide of procollagen type I is an independent predictor of diastolic function in patients with advanced systolic heart failure. Congest Heart Fail. 2008; 14(6): 302–306.
  17. Rossi A, Cicoira M, Golia G, et al. Amino-terminal propeptide of type III procollagen is associated with restrictive mitral filling pattern in patients with dilated cardiomyopathy: a possible link between diastolic dysfunction and prognosis. Heart. 2004; 90(6): 650–654.
  18. Glazer NL, Macy EM, Lumley T, et al. Transforming growth factor beta-1 and incidence of heart failure in older adults: the Cardiovascular Health Study. Cytokine. 2012; 60(2): 341–345.
  19. Hein S, Arnon E, Kostin S, et al. Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: structural deterioration and compensatory mechanisms. Circulation. 2003; 107(7): 984–991.
  20. Khan SA, Joyce J, Tsuda T. Quantification of active and total transforming growth factor-β levels in serum and solid organ tissues by bioassay. BMC Res Notes. 2012; 5: 636.
  21. Petrov VV, Fagard RH, Lijnen PJ. Stimulation of collagen production by transforming growth factor-beta1 during differentiation of cardiac fibroblasts to myofibroblasts. Hypertension. 2002; 39(2): 258–263.
  22. Accornero F, van Berlo JH, Correll RN, et al. Genetic Analysis of Connective Tissue Growth Factor as an Effector of Transforming Growth Factor β Signaling and Cardiac Remodeling. Mol Cell Biol. 2015; 35(12): 2154–2164.
  23. Wu CK, Wang YC, Lee JK, et al. Connective tissue growth factor and cardiac diastolic dysfunction: human data from the Taiwan diastolic heart failure registry and molecular basis by cellular and animal models. Eur J Heart Fail. 2014; 16(2): 163–172.
  24. de Boer RA, Yu L, van Veldhuisen DJ. Galectin-3 in cardiac remodeling and heart failure. Curr Heart Fail Rep. 2010; 7(1): 1–8.
  25. Wu CK, Su MY, Lee JK, et al. Galectin-3 level and the severity of cardiac diastolic dysfunction using cellular and animal models and clinical indices. Sci Rep. 2015; 5: 17007.
  26. Gurel OM, Yilmaz H, Celik TH, et al. Galectin-3 as a new biomarker of diastolic dysfunction in hemodialysis patients. Herz. 2015; 40(5): 788–794.
  27. Michalski B, Trzciński P, Kupczyńska K, et al. The differences in the relationship between diastolic dysfunction, selected biomarkers and collagen turn-over in heart failure patients with preserved and reduced ejection fraction. Cardiol J. 2017; 24(1): 35–42.
  28. Ommen SR, Nishimura RA, Appleton CP, et al. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: A comparative simultaneous Doppler-catheterization study. Circulation. 2000; 102(15): 1788–1794.
  29. Besler C, Lang D, Urban D, et al. Plasma and cardiac galectin-3 in patients with heart failure reflects both inflammation and fibrosis: implications for its use as a biomarker. Circ Heart Fail. 2017; 10(3).

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