title: Fibrosis of extracellular matrix is related to the duration of the disease but is unrelated to the dynamics of collagen metabolism in dilated cardiomyopathy.
abstract: BACKGROUND
  Fibrosis of extracellular matrix (ECM) in dilated cardiomyopathy (DCM) corresponds to the myocardial over-production of various types of collagens. However, mechanism of this process is poorly understood.
  
  
  OBJECTIVE
  To investigate whether enhanced metabolism of ECM occur in DCM.
  
  
  METHODS
  Seventy consecutive DCM patients (pts) (48 ± 12.1 years, EF 24.4 ± 7.4 %) and 20 healthy volunteers were studied. Based on symptoms duration, pts were divided into new-onset (n = 35, 6 months) and chronic DCM (n = 35, >6 months). Markers of collagen type I and III synthesis-procollagen type I carboxy- and amino-terminal peptides (PICP and PINP) and procollagen type III carboxy- and amino-terminal peptides (PIIICP and PIIINP), collagen 1 (col-1), ECM metabolism controlling factors-tumor growth factor beta-1 (TGF1-β), connective tissue growth factor (CTGF), and ECM degradation enzymes-matrix metalloproteinases (MMP-2, MMP-9) and their tissue inhibitor (TIMP-1) were measured in serum. All pts underwent right ventricular endomyocardial biopsy to study ECM fibrosis.
  
  
  RESULTS
  The presence of fibrosis was detected in 24 (34.3 %) pts and was more prevalent in chronic DCM [17 (48.6 %) vs. 7 (20 %), p < 0.01]. The levels of PIIINP [4.41 (2.17-6.08) vs. 3.32 (1.69-5.02) ng/ml, p < 0.001], CTGF [3.82 (0.48-23.87) vs. 2.37 (0.51-25.32) ng/ml, p < 0.01], MMP-2 [6.06 (2.72-14.8) vs. 4.43 (2.27-7.4) ng/ml, p < 0.001], MMP-9 [1.98 (0.28-9.25) vs. 1.01 (0.29-3.59) ng/ml, p < 0.002)], and TIMP-1 [15.29 (1.8-36.17) vs. 2.61 (1.65-24.09) ng/ml, p < 0.004] were significantly higher in DCM, whereas levels of col-1 [57.7 (23.1-233.4) vs. 159.4 (31.2-512.9) pg/ml, p < 0.001] were significantly lower in DCM compared to controls. There were no differences in all measured serum markers of ECM metabolism between newonset and chronic DCM and as well as fibrosis positive and negative pts. Fibrosis was weakly correlated only with the duration of DCM (r = 0.23, p < 0.05), however, not a single serum marker of fibrosis correlated with fibrosis. Neither unadjusted nor adjusted models, constructed from serum markers of ECM metabolism, predicted the probability of myocardial fibrosis.
  
  
  CONCLUSIONS
  Dynamics of ECM turnover in DCM is high, which is reflected by the increased levels CTGF and degradation enzymes. Synthesis of collagen type III prevailed over collagen type I. ECM metabolism was not different in DCM regardless of the duration of the disease and status of myocardial fibrosis. Serum markers of ECM metabolism were found not to be useful for the prediction of myocardial fibrosis in DCM.
authors: Department of Cardiac and Vascular Diseases, John Paul II Hospital, Pradnicka St. 80, 31-202, Krakow, Poland. pawelrub@poczta.onet.pl.
authors: Paweł
authors: http://orcid.org/0000-0002-6979-3411
authors: P
authors: Rubiś
authors: Department of Cardiac and Vascular Diseases, John Paul II Hospital, Pradnicka St. 80, 31-202, Krakow, Poland.
authors: Sylwia
authors: S
authors: Wiśniowska-Śmialek
authors: Department of Molecular Biology, John Paul II Hospital, Pradnicka St. 80, Krakow, Poland.
authors: Ewa
authors: E
authors: Wypasek
authors: Department of Cardiac and Vascular Diseases, John Paul II Hospital, Pradnicka St. 80, 31-202, Krakow, Poland.
authors: Barbara
authors: B
authors: Biernacka-Fijalkowska
authors: Department of Pathology, John Paul II Hospital, Pradnicka St. 80, 31-202, Krakow, Poland.
authors: Lucyna
authors: L
authors: Rudnicka-Sosin
authors: Jagiellonian University Medical College, Saint Ann St. 12, 31-008, Krakow, Poland.
authors: Ewa
authors: E
authors: Dziewiecka
authors: Jagiellonian University Medical College, Saint Ann St. 12, 31-008, Krakow, Poland.
authors: Patrycja
authors: P
authors: Faltyn
authors: Jagiellonian University Medical College, Saint Ann St. 12, 31-008, Krakow, Poland.
authors: Lusine
authors: L
authors: Khachatryan
authors: Jagiellonian University Medical College, Saint Ann St. 12, 31-008, Krakow, Poland.
authors: Aleksandra
authors: A
authors: Karabinowska
authors: Department of Cardiac and Vascular Diseases, John Paul II Hospital, Pradnicka St. 80, 31-202, Krakow, Poland.
authors: Artur
authors: A
authors: Kozanecki
authors: Department of Cardiac and Vascular Diseases, John Paul II Hospital, Pradnicka St. 80, 31-202, Krakow, Poland.|Jagiellonian University Medical College, Saint Ann St. 12, 31-008, Krakow, Poland.
authors: Lidia
authors: L
authors: Tomkiewicz-Pająk
authors: Department of Cardiac and Vascular Diseases, John Paul II Hospital, Pradnicka St. 80, 31-202, Krakow, Poland.|Jagiellonian University Medical College, Saint Ann St. 12, 31-008, Krakow, Poland.
authors: Piotr
authors: P
authors: Podolec
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002311:Cardiomyopathy, Dilated / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000097:blood; D005109:Extracellular Matrix / Q000473:pathology*; D005260:Female; D005355:Fibrosis; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D016212:Transforming Growth Factor beta / Q000097:blood
chemical_list: D015415:Biomarkers; C526317:CCN2 protein, human; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; D003094:Collagen; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Biopsy; Collagen; Dilated cardiomyopathy; Extracellular matrix; Fibrosis; Markers