FGF13 attenuates myocardial infarction-induced cardiac injury by modulating oxidative stress and NF-κB signaling

Myocardial infarction (MI) is a major cause of heart failure characterized by cardiomyocyte loss, adverse remodeling, and oxidative stress, with limited effective therapeutic targets. Fibroblast growth factor 13 (FGF13), an intracellular FGF family member, has not been fully explored in MI. Integrated transcriptomic analyses, including single-cell and bulk RNA sequencing datasets, revealed that FGF13 is predominantly expressed in cardiomyocytes and is downregulated following MI. In an MI model with AAV-mediated FGF13 overexpression, FGF13 improved cardiac function, as evidenced by increased ejection fraction and fractional shortening, reduced ventricular dilation, and attenuated fibrosis and apoptosis in vivo. In vitro, hypoxia decreased FGF13 expression in a time-dependent manner, accompanied by increased reactive oxygen species (ROS) and activation of NF-κB signaling. FGF13 overexpression reduced ROS accumulation, suppressed p65 phosphorylation, and restored SOD2 expression. Moreover, TNF-α-induced NF-κB activation promoted oxidative stress, whereas FGF13 partially reversed these effects. Collectively, FGF13 alleviates MI-induced cardiac injury and adverse remodeling, accompanied by reduced oxidative stress and NF-κB activation, highlighting its potential role in the response to ischemic cardiac injury.