Angiotensin II promotes integrin-mediated collagen gel contraction by adult rat cardiac fibroblasts

Remodeling is a fundamental cardiac response to injury and involves cardiac fibroblast proliferation and extracellular matrix (ECM) production. Angiotensin II (Ang II) directly promotes these changes in cardiac fibroblasts and thus, plays critical roles in cardiac hypertrophy and wound healing. Osteopontin, fibronectin and laminin mRNA were detected in total RNA harvested from cultured adult rat cardiac fibroblasts. Immunocytochemistry staining of cultured adult rat cardiac fibroblasts grown on coverslips revealed the presence of beta 3 integrins on the surfaces of the cells. In the present study, we investigated the role of Ang II in a model of wound repair using floating collagen gels harboring adult rat cardiac fibroblasts, and we determined which members of the integrin family existed on these cells. The presence of either MPIIIB10, a monoclonal antibody against osteopontin (7.2 micrograms/ml) or RGD (arginine-glycine-aspartate) peptide (10(4) M) had no effect on gel contraction. Osteopontin itself induced gel contraction; however this effect was completely neutralized by MPIIIB10 (7.2 micrograms/ml, RGD peptide (10(4) M) and a monoclonal antibody against rat beta 3 integrin (25 micrograms/ml). We identified alpha v, beta 3 and beta 5 integrins on adult rat cardiac fibroblasts by fluorescence-activated cell sorting and confirmed that RGD peptide and an antibody against beta 3 integrin completely blocked osteopontin-induced gel contraction. These results suggest that Ang II promotes cardiac wound healing and remodeling processes by inducing expression of osteopontin and beta 3 integrin by cardiac fibroblasts.