Abstract
Cardiac fibrosis is the final event of heart failure and is associated with almost all forms of cardiovascular disease. Cardiac fibroblasts (CFs), a major cell type in the heart, are responsible for regulating normal myocardial function and maintaining extracellular matrix homeostasis in adverse myocardial remodeling. In this study, we found that C188-9, a small-molecule inhibitor of signal transducer and activator of transcription 3 (STAT3), exhibited an antifibrotic function, both in vitro and in vivo. C188-9 decreased transforming growth factor-β1-induced CF activation and fibrotic gene expression. Moreover, C188-9 treatment alleviated heart injury and cardiac fibrosis in an isoproterenol-induced mouse model by suppressing STAT3 phosphorylation and activation. These findings may help us better understand the role of C188-9 in cardiac fibrosis and facilitate the development of new treatments for cardiac fibrosis and other cardiovascular diseases.