@Article{,
AUTHOR = {Dimitrios Tziakas, Georgios Chalikias, John T. Parissis, Helen Hatzinikolaou, Dimitrios Stakos, Evropi Papadopoulou, Alexandros Kortsaris, Dimitrios Hatseras},
TITLE = {Prolonged activation of Tumor necrosis factor (TNF)-α and its soluble receptors in chronic heart failure patients both in the compensated and decompensated state. Interplay between their levels and metalloproteinase-3},
JOURNAL = {European Cytokine Network},
VOLUME = {15},
YEAR = {2004},
NUMBER = {3},
PAGES = {231--239},
URL = {http://www.techscience.com/ECN/v15n3/66379},
ISSN = {1952-4005},
ABSTRACT = {Introduction. Recent clinical and experimental studies indicate that upregulation of the TNF system
can contribute to the progression of cardiac remodeling and heart failure decompensation, by promoting
alterations in cardiomyocyte biology and extracellular matrix metabolism. Extracellular matrix turnover is
regulated by the matrix metalloproteinases (MMPs), which are endogenous enzymes responsible for extracellular
collagen degradation. The present study investigates the fluctuation of serum levels of TNF-α, soluble TNF
receptor-1 (sTNFR1) and -2 (sTNFR2), in patients with chronic heart failure both during acute decompensation
and the stable state of the syndrome. The second goal of this study was to determine if a relationship exists
between serum MMPs profiles (MMP-1, MMP-2, MMP-3) and circulating TNF-α or its soluble receptors.
Methods. Our patient group consisted of 52 patients with chronic heart failure (NYHA III-IV; mean age:
65 ± 4 years; hypertensive cardiomyopathy: 20, ischemic cardiomyopathy: 17, dilated cardiomyopathy: 10,
valvular disease: 5), who were hospitalized for acute decompensation of the syndrome. Our control group
consisted of 30 healthy subjects (mean age: 57 ± 6 years). Serum levels of TNF-α, sTNFR1, sTNFR2 and
MMP-1,-2,-3 were measured in heart failure patients by ELISA at admission and after one month as follow-up.
Values are expressed as medians and interquartile ranges. {|ital}Results. In our patient group, we observed a
statistically significant increase in the levels of sTNFR1 and sTNFR2 at admission (sTNFR1: 5.15 ng/mL,
4.49-8.90 ng/mL, P < 0.001, sTNFR2: 13.40 ng/mL, 6.10-21.50 ng/mL, P < 0.001), and at one-month follow-up
(sTNFR1: 5.30 ng/mL, 4.61-6.90 ng/mL, P < 0.001, sTNFR2: 21.80 ng/mL, 11.50-25.20 ng/mL, P < 0.001),
compared to the control group (sTNFR1: 3.83 ng/mL, 3.70-3.95 ng/mL, sTNFR2: 4.00 ng/mL, 3.40-5.40 ng/mL).
There was a statistically significant difference in the levels of sTNFR2 between admission and follow-up (P < 0.05).
Significant correlations between serum MMP-3 and sTNFR2 levels both at admission and follow up (r = 0.460,
P = 0.005 and r = 0.338, P = 0.044, respectively) were also found. Conclusions. Soluble TNF receptors are elevated
in heart failure patients both in acute decompensation and stable phase. We have detected higher levels of soluble
TNFR2 during the compensated phase of heart failure, suggesting that TNFR2 receptors appear to stabilize the
cytokine and thereby prolong its half-life and biological functions. Finally, TNF system - mediated cardiac
remodeling may exist through the activation of MMP-3 signaling pathways.},
DOI = {}
}