Src tyrosine kinase promotes cardiac remodeling induced by chronic sympathetic activation

Cardiac remodeling serves as the underlying pathological basis for numerous cardiovascular diseases and represents a pivotal stage for intervention. The excessive activation of beta-adrenergic receptors (beta-ARs) assumes a crucial role in cardiac remodeling. Nonetheless, the underlying molecular mechanisms governing beta-AR-induced cardiac remodeling remain largely unresolved. In the present study, we identified Src tyrosine kinase as a key player in the cardiac remodeling triggered by excessive beta-AR activation. Our findings demonstrated that Src mediates isoproterenol (ISO)-induced cardiac hypertrophy, fibrosis, and inflammation in vivo. Furthermore, Src facilitates beta-AR-mediated proliferation and transdifferentiation of cardiac fibroblasts, and hypertrophy and cardiomyocytes in vitro. Subsequent investigations have substantiated that Src mediates beta-AR induced the extracellular signal-regulated protein kinase (ERK1/2) signaling pathway activated by beta-AR. Our research presents compelling evidence that Src promotes beta-AR-induced cardiac remodeling in both in vivo and in vitro settings. It establishes the promoting effect of the beta-AR/Src/ERK signaling pathway on overall cardiac remodeling in cardiac fibroblasts and underscores the potential of Src as a therapeutic target for cardiac remodeling.

Automated summary

This study identifies Src tyrosine kinase as a key player in cardiac remodeling triggered by excessive beta-adrenergic receptor activation. Src mediates isoproterenol-induced cardiac hypertrophy, fibrosis, and inflammation in vivo, as well as proliferation and transdifferentiation of cardiac fibroblasts and hypertrophy of cardiomyocytes in vitro. It also mediates the extracellular signal-regulated protein kinase signaling pathway activated by beta-adrenergic receptor. These findings highlight the potential of Src as a therapeutic target for cardiac remodeling.