Differential responses of adult cardiac fibroblasts to in vitro biaxial strain patterns

Different patterns of extracellular matrix (FCM) remodeling in the heart ar e thought to be dependent on altered mechanical and chemical conditions and can contribute to cardiac dysfunction. Cardiac fibroblasts are the primary regulators of the ECM and may respond to mechanical factors in vitro. We h ypothesized that different types of in vitro strains, e.g. tensile or compr essive. call stimulate different functional responses in cultured adult rat cardiac fibroblasts. In this study, we first showed that a single step in strain applied by a uniaxial stretch system stimulated collagen III and fib ronectin mRNA levels and transforming growth factor-beta(1) (TGF-beta(1)) a ctivity in the adult phenotype of rat cardiac fibroblasts. Two-dimensional deformations were measured by tracking fluorescent microspheres attached to the substrate and cultured cells. For 10% uniaxial strain, mean principal strains were 0.104+/-0.018 in the direction of stretch and -0.042+/-0.013 i n the perpendicular direction, verifying that the fibroblasts were simultan eously subjected to tensile (positive) and compressive (negative) strains. Furthermore, these cells were also subjected to area change and to shear, I n order to examine the distinct effects of different types of deformation o n cardiac fibroblasts, an equibiaxial stretch system was used to apply eith er pure tensile or compressive area strains, in the absence of shear. Magni tudes of equibiaxial strain were selected to apply local cell area changes identical to those applied in the uniaxial system. Results showed that pure tensile and compressive area strains induced divergent responses in ECM mR NA levels. TGF-beta(1) activity was dependent on the magnitude of applied a rea strain regardless of the mode of deformation. These findings demonstrat e that;adult cardiac fibroblasts may respond differently to varied types of mechanical loading, suggesting that ECM remodeling may be locally regulate d by specific mechanical stimuli in the heart. (C) 1999 Academic Press.