gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

Relevance of myocardial inflammation for remodeling of the extracellular matrix in patients with inflammatory cardiomyopathy

Relevanz der myokardialen Entzündung für das Remodeling der extrazelluläre Matrix bei inflammatorischer Kardiomyopathie

Meeting Abstract (Hypertonie 2003)

  • presenting/speaker K. Hoppe - Universitätsmedizin Berlin (Berlin, D)
  • F. Reichenbach - Universitätsmedizin Berlin (Berlin, D)
  • C. Skurk - Universitätsmedizin Berlin (Berlin, D)
  • M. Noutsias - Universitätsmedizin Berlin (Berlin, D)
  • J. Li - Universitätsmedizin Berlin (Berlin, D)
  • H.P. Schultheiss - Universitätsmedizin Berlin (Berlin, D)
  • M. Pauschinger - Universitätsmedizin Berlin (Berlin, D)

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. Düsseldorf, Köln: German Medical Science; 2004. Doc03hochP68

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hoch2003/03hoch168.shtml

Published: November 11, 2004

© 2004 Hoppe et al.
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Outline

Text

Problem

The disruption of the extracellular matrix by matrix metalloproteinases (MMPs) plays a key role in myocardial remodeling in heart failure. However, the mechanisms for MMP expression are still unknown. In this study we analyzed the relevance of chronic myocardial inflammation in patients with inflammatory dilated cardiomyopathy (infDCM) for induction of MMP expression.

Study Design and Methods

15 patients with the clinically suspected diagnosis of DCM (mean EF 33±12%) were enrolled in this study. 9 patients with locoregional left ventricular dysfunction (EF 69±5%) served as a control. Endomyocardial biopsies of all 24 patients were analyzed by histological (Dallas criteria) and immunohistological techniques (CD3-T-lymphocyte infiltration) for the degree of myocardial inflammation. Semi-quantitative RT-PCR were performed for the evaluation of mRNA abundance of MMP-3 and tissue inhibitor of MMP-3 (TIMP-4). Data were analyzed using MANOVA and LSD test.

Results

None of the patients were classified as active or borderline myocarditis. However, 7/15 with DCM were classified as infDCM with significantly increased CD3-T-lymphocytes/high power field (mean ± SD: 3,40±2,97vs. 0,53±0,28). In patients with infDCM compared to controls a significant upregulated MMP-3 abundance (0,91±0,84 vs. 0,27±0,20) was associated with a significant downregulation of TIMP-4 (0,63±0,33 vs. 0,89±0,10). However, in DCM patients without significant T-lymphocytic infiltrates compared with controls there was no significant difference in MMP-3 (0,39±0,33 vs. 0,27±0,20) and TIMP-4 (0,75±0,13 vs. 0,89±0,10) mRNA abundance.

Conclusions

Chronic myocardial inflammation in infDCM is associated with an increased MMP-3 mRNA abundance without a counterbalance of TIMP-4 expression. This imbalance might constitute a key factor for the progression of left ventricular function in these patients, which might have major therapeutic implications (e.g. immunosuppressive therapy, inhibition of MMP).