Src tyrosine kinase promotes cardiac remodeling induced by chronic sympathetic activation

Abstract

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