Left ventricular dilation and myocardial remodeling are hallmarks of
dilated cardiomyopathy (DCM). It is assumed that left ventricular dilation is caused by the disintegration of the collagenous network by increased collagenolytic activity of
matrix metalloproteinases (
MMPs) and their adequate tissue inhibitors (TIMPs). In this study the myocardial MMP-1 and
TIMP-1 mRNA expressions were investigated by using real-time quantitative PCR analysis from right septal endomyocardial biopsies of patients with
dilated cardiomyopathy (n = 46) and control subjects (n = 11). The volume density (Vv%) of
collagen was measured morphometrically. Classification was done according to LV diameters [left ventricular enddiastolic diameter (LVEDD, cm) calculated to body surface area (BSA, m(2))] into three DCM groups: group I (LVEDD-BSA > 2.7-3.0 cm/m(2)), group II ( > 3.0-3.6 cm/m(2)), group III ( > 3.6 cm/m(2)), controls (< 2.7 cm/m(2)). Compared with controls, the MMP-1 expression in patients with DCM was significantly increased (119.2 +/- 45.2 vs. 1.3 +/- 0.4; p < 0.001) as was
TIMP-1 expression (9.6 +/- 1.2 vs. 1.3 +/- 0.4; p < 0.01). Moreover the MMP-1 and
TIMP-1 expression varied according to LV diameter: group I (
MMP-1: 8.7 +/- 3.5; p = 0.33; TIMP- 1: 4.5 +/- 1.2; p < 0.01); group II (
MMP-1: 211.4 +/- 86.0; p < 0.001; TIMP-1: 12.5 +/- 1.9 ; p < 0.001); group III (
MMP-1: 38.8 +/- 22.6; p < 0.01; TIMP-1: 8.1 +/- 1.7; p < 0.001). Compared with controls, the
collagen level in DCMPt. was significantly increased: 5.0 +/- 0.6 vol% vs 1.2 +/- 0.2 vol% p < 0.001 and correlates with LV diameter. This study reveals that the overexpression of MMP-1, which is associated with an increased ratio of
MMP-1/TIMP-1 in DCM, indicates an activated collagenolytic system while replacement
fibrosis is accumulating. The MMP-1 overexpression is mainly found in moderately dilated DCM hearts (group II) indicating the dynamic process of LV dilation and the importance of
collagenases in the early phase of LV remodeling.