Abstract 2188: Imbalance In The Mmp timp-system And Myocardial Fibrosis In Patients With Inflammatory Cardiomyopathy
Introduction: Inflammation and/or viral infection are both relevant for extracellular matrix remodeling. Therefore the effects of myocardial inflammation on ECM remodeling are analyzed in this study.
# Methods and results: Endomyocardial biopsies were obtained from 20 patients with established DCM (2.11±0.44 CD3 cells/mm2) and 29 DCMi patients (18.91±6.41 CD3 cells/mm2) comparable in age (51.45±3.15 vs. 48.48±2.39 years), LVEDD (72.7±2.2 vs. 69.76±1.06mm) and EF (26±2.99 vs. 25.86±2.0%). Total collagen content was quantified by picosiriusredstaining while the MMP2, MMP3 and TIMP1 expression was evaluated by immunohistochemistry. The MMP1, MMP3 and TIMP1 and ICTP expression in the serum was quantified by Elisa. and levels of IL6 and IL8 were measured by BioPlexAssays. Furthermore various cytokines and proteases were evaluated by real-time-PCR. In DCMi patients both CD3-lymphocyte infiltration (8.95fold, p<0.001) and IL6 expression (2.93fold, p=0.0067) were significantly increased vs. DCM as well as the mRNA-expression of TNF-alpha (p<0,049). The cellular inflammation correlated with the grade of fibrosis (p<0.01) which is 2.43fold elevated in DCMi (p<0.01). This may be caused by the increased MMP expression in DCMi, demonstrated by elevated MMP1 serum level (1.64fold increased, p<0.01 vs. DCM) and slightly increased MMP-2 (1.41fold) and MMP-3 (1.6fold) expression in biopsies. In contrast, the serum levels of TIMP1 were reduced to 83.14% in DCMi (p=0.06 vs. DCM) and correlated negatively to the serum MMP3 expression (p<0.01) indicating an imbalance in the proteasessystem. The transcripts amount of collagen type I (ρ = −0.80; P<0.0091) and III (ρ = −0.80; P<0.0091), inflammatory cytokines TGF beta (ρ =−0.67; P<0.044) and INF beta (ρ = −0.47; P<0.05) as well amount of ICTP (ρ = −0.89; P<0.0011) was positively correlated with decreased LVEF from DCMi patients. The increased number of CD3 active cells in DCM biopsies was positively linked to the protein amount of TIMP1 as well to the mRNA amount of MMP9.
Conclusion: Myocardial inflammation in patients with DCMi leads to an imbalance in the MMP/TIMP-system, which attributes to the development of myocardial fibrosis.