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Fibrosis of extracellular matrix is related to the duration of the disease but is unrelated to the dynamics of collagen metabolism in dilated cardiomyopathy
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:...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075017/ https://www.ncbi.nlm.nih.gov/pubmed/27516211 http://dx.doi.org/10.1007/s00011-016-0977-3 |
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author | Rubiś, Paweł Wiśniowska-Śmialek, Sylwia Wypasek, Ewa Biernacka-Fijalkowska, Barbara Rudnicka-Sosin, Lucyna Dziewiecka, Ewa Faltyn, Patrycja Khachatryan, Lusine Karabinowska, Aleksandra Kozanecki, Artur Tomkiewicz-Pająk, Lidia Podolec, Piotr |
author_facet | Rubiś, Paweł Wiśniowska-Śmialek, Sylwia Wypasek, Ewa Biernacka-Fijalkowska, Barbara Rudnicka-Sosin, Lucyna Dziewiecka, Ewa Faltyn, Patrycja Khachatryan, Lusine Karabinowska, Aleksandra Kozanecki, Artur Tomkiewicz-Pająk, Lidia Podolec, Piotr |
author_sort | Rubiś, Paweł |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5075017 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-50750172016-11-04 Fibrosis of extracellular matrix is related to the duration of the disease but is unrelated to the dynamics of collagen metabolism in dilated cardiomyopathy Rubiś, Paweł Wiśniowska-Śmialek, Sylwia Wypasek, Ewa Biernacka-Fijalkowska, Barbara Rudnicka-Sosin, Lucyna Dziewiecka, Ewa Faltyn, Patrycja Khachatryan, Lusine Karabinowska, Aleksandra Kozanecki, Artur Tomkiewicz-Pająk, Lidia Podolec, Piotr Inflamm Res Original Research Paper 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. Springer International Publishing 2016-08-11 2016 /pmc/articles/PMC5075017/ /pubmed/27516211 http://dx.doi.org/10.1007/s00011-016-0977-3 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Research Paper Rubiś, Paweł Wiśniowska-Śmialek, Sylwia Wypasek, Ewa Biernacka-Fijalkowska, Barbara Rudnicka-Sosin, Lucyna Dziewiecka, Ewa Faltyn, Patrycja Khachatryan, Lusine Karabinowska, Aleksandra Kozanecki, Artur Tomkiewicz-Pająk, Lidia Podolec, Piotr Fibrosis of extracellular matrix is related to the duration of the disease but is unrelated to the dynamics of collagen metabolism in dilated cardiomyopathy |
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 |
title_full | Fibrosis of extracellular matrix is related to the duration of the disease but is unrelated to the dynamics of collagen metabolism in dilated cardiomyopathy |
title_fullStr | Fibrosis of extracellular matrix is related to the duration of the disease but is unrelated to the dynamics of collagen metabolism in dilated cardiomyopathy |
title_full_unstemmed | Fibrosis of extracellular matrix is related to the duration of the disease but is unrelated to the dynamics of collagen metabolism in dilated cardiomyopathy |
title_short | Fibrosis of extracellular matrix is related to the duration of the disease but is unrelated to the dynamics of collagen metabolism in dilated cardiomyopathy |
title_sort | fibrosis of extracellular matrix is related to the duration of the disease but is unrelated to the dynamics of collagen metabolism in dilated cardiomyopathy |
topic | Original Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075017/ https://www.ncbi.nlm.nih.gov/pubmed/27516211 http://dx.doi.org/10.1007/s00011-016-0977-3 |
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