Transforming growth factor-beta1-mediated collagen gel contraction by cardiac fibroblasts

The aim of this study was to determine whether the ability of TGF-beta1 to affect the contractile activity of cardiac fibroblasts depends on their differentiation into myofibroblasts. Cardiac fibroblasts (from male adult Wistar rats) from passage 2 were cultured to confluency and incubated on a hydrated collagen gel with and without TGF-beta1 (0, 20, 40, 100, 200 or 600 pmol/l) for 1, 2 and 3 days in a Dulbecco's Modified Eagle's Medium without foetal bovine serum.The area of the collagen gel was determined by densitometric analysis. TGF-beta1 dose-dependently increased the contraction of collagen gel mediated by cardiac fibroblasts, reaching a maximal effect at 100 pmol/L. TGF-beta1 also stimulated tritium-thymidine incorporation and total protein content in cardiac fibroblasts in the collagen gel lattice. TGF-beta1 dose-dependently induced an increase in alpha-smooth muscle actin, a marker of myofibroblasts. The TGF-beta1-induced reduction of the area of the collagen gel was negatively correlated with the TGF-beta1-evoked appearance of alpha-smooth muscle actin in the collagen gel matrix. Our data demonstrate that TGF-beta1 increased the contractile activity of adult rat cardiac fibroblasts and their ability to differentiate into myofibroblasts. Because contractile activity was correlated with differentiation, the influence of TGF-beta1 on cardiac fibroblast-induced collagen gel contraction might depend on the promotion of myofibroblast differentiation. Am J Hypertens (2004) 17, 173A–173A; doi: 10.1016/j.amjhyper.2004.03.454