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Background TGF-β[sub 1] mediates effects on fibroblast proliferation and collagen synthesis in the myocardium. The extracellular matrix remodeling depends on the fibrillar collagen degrading matrix metalloproteinases (MMPs) and their inhibitors (TIMPs).The in vivo effects of TGFβ[sub 1]on the MMP/TIMP system in TGF-beta;[sub 1] overexpressing transgenic mice were studied. Methods MaleAlb/TGF-β[sub 1](cys[sup 223,225]ser) transgenic mice (TG) and nontransgenic controls (C; 8 weeks) were examined. Protein expression of collagen type I, -III, interstitial collagenase (Int Coil), MMP-2,-9, TIMP-1,-2,-4 and TGF-β[sub 1] as well as enzyme activity (MMP-2, -9) were measured (Western blots, zymographic assays), mRNA expression of the interstitial collagenase and MMP-9 was studied with the Light-Cycler based real-time PCR. Results Overexpression of TGF-β[sub 1] resulted in a 10-fold increase in plasma and a sevenfold increase in myocardial TGF-β[sub 1] concentrations. Relative heart weights increased (mg g[sup -l]: 7·8 ± 0·4 vs. 4·8 ± 0·6, n = 6; P < 0·01) in TG compared to C. Collagen type I and III increased inTG (1·9-fold and 1·7-fold) compared to controls. Interstitial collagenase protein activity (-91%) and mRNA expression (-75%) inTG were reduced (P < 0·05-P < 0·001). Gelatinase (MMP-2, MMP-9) expression and activity were not significantly alterated. MMPinhibitors were increased 2·5-fold (TIMP-1, -4) and 6-fold (TIMP-2) in TG. Conclusions TGF-β[sub 1] produces myocardial fibrosis in vivo. This effect is not only produced by a stimulation of matrix protein formation: a complex regulation of MMP and TIMP interaction, namely decrease of expression and activity of interstitial collagenase and an enhanced inhibition by increased levels of TIMPs, are involved. These mechanisms are optional targets for therapeutic interventions in myocardial diseases. [ABSTRACT FROM AUTHOR]