Differential integrin expression by cardiac fibroblasts from hypertensive and exercise-trained rat hearts.
The cardiac fibroblast is the principal cell type responsible for extracellular matrix (ECM) synthesis in the heart during growth and pathophysiological conditions. A dynamic interaction exists between the cardiac ECM and fibroblasts that is sensitive to the local mechanical and chemical tissue environment. We propose here that cardiac fibroblasts structurally and functionally adapt to changing local environments by altering their expression of receptor integrins. Changes in the extracellular environment are communicated in part by integrins, which link the ECM to the cell and regulate phenotype and function. In this report, we analyze integrin protein expression, migration and gel contraction by cardiac fibroblasts from rats subjected to 10 weeks of treadmill exercise (XTR), experimental hypertension (HYP) or controls (CONT). Immunoprecipitation shows that beta1 protein increases in XTR and HYP. Also, alpha1 and alpha2 integrins are lower in XTR and HYP, and alpha5 integrin is higher in XTR and lower in HYP. Functional assays show that XTR and HYP migrate slower on collagen, while XTR migrate faster and HYP slower on fibronectin. Cell isolation procedure, population expansion number or a general adaptation to culture conditions does not explain the differences observed. No significant differences in collagen gel contraction are detected. These results indicate that cardiac fibroblasts retain their in vivo patterns in vitro for a limited number of population expansions. This tissue-specific phenotype is exhibited in early passage (< or =6). However, by late passage (>8), cells begin to show adaptation to the in vitro conditions. These results show that cardiac fibroblasts respond to changing environments in pathophysiological conditions by modulating integrin expression, which is associated with changes in cell migration. They also suggest a pragmatic use for primary cardiac fibroblasts as a model to study the cardiac matrix remodeled by physiological (exercise) and pathological (hypertension) stressors.