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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Inflamm+Res
2016 ; 65
(12
): 941-949
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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
#MMPMID27516211
Rubi? P
; Wi?niowska-?mialek S
; Wypasek E
; Biernacka-Fijalkowska B
; Rudnicka-Sosin L
; Dziewiecka E
; Faltyn P
; Khachatryan L
; Karabinowska A
; Kozanecki A
; Tomkiewicz-Paj?k L
; Podolec P
Inflamm Res
2016[Dec]; 65
(12
): 941-949
PMID27516211
show ga
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-?), 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.