Cxcl1 as a central regulator of NET formation, cardiomyocyte apoptosis, and fibroblast proliferation in the shared pathogenesis of MR, DCM, and AF.

Mitral regurgitation (MR), dilated cardiomyopathy (DCM), and atrial fibrillation (AF) are interconnected cardiac conditions characterized by cardiomyocyte apoptosis and pathological fibroblast proliferation. Neutrophil extracellular traps (NETs) promote these processes, but their role in MR, DCM, and AF remains unclear. Here, we identified Cxcl1 as a common gene in MR, DCM, and AF via bioinformatics analysis. Functional assays showed that Cxcl1 induces NET formation, which subsequently enhances cardiomyocyte apoptosis and fibroblast proliferation. Mechanistically, Cxcl1 activates AKT phosphorylation, driving NET-mediated cardiac remodeling. Targeting Cxcl1 may break the self-reinforcing cycle in these diseases.