ANGIOTENSIN-II PROMOTES REMODELING-RELATED EVENTS IN CARDIAC FIBROBLASTS

Remodelling is a fundamental cardiac response to injury, and involves cardiac fibroblast proliferation and extracellular matrix production. Angiotensin II (A II) directly promotes these changes in cardiac fibro blasts, and is thus a critical element in cardiac hypertrophy and a pr ocessor of wound healing. Osteopontin mRNA was readily detectable in t otal RNA harvested from cultured neonatal and adult cardiac fibroblast s. Immunocytochemical staining of cultured adult cardiac fibroblasts g rown on coverslips revealed the presence of beta(3) integrin on the su rfaces of the cells. In the present study, we investigated the role of A II in a model of wound healing using floating collagen gels harbori ng adult rat cardiac fibroblasts. The presence of a monoclonal antibod y against osteopontin, MPIIIB10, at 7.2 mu g/ml, or the arginine-glyci ne-aspartate (RGD) peptide (10(-4)M), had no effect on gel contraction . Osteopontin itself induced fibroblast gel contraction (79.1 +/- 3.8% ). But this effect of osteopontin was completely neutralized by MPIIIB 10 (7.2 mu g/ml), RGD peptide (10(-4)M), and monoclonal antibody again st rat beta(3) integrin (25 mu g/ml). These results suggest that A II promotes cardiac wound hearing and remodelling processes by inducing o steopontin and beta(3) integrin in cardiac fibrobalsts.