RhoA/ROCK1 aggravates transverse aortic constriction-induced atrial fibrillation by enhancing NF-κBp65/CCL2 signaling pathway.

Atrial fibrillation (AF) is closely associated with atrial electrical and structural remodeling, yet effective pharmacological treatment strategies remain limited. The Ras homolog gene family member A (RhoA) and its downstream effector rho-kinase 1 (ROCK1) act as central regulators of cytoskeletal dynamics and inflammatory signaling. However, the mechanism of the RhoA/ROCK1 signaling pathway in atrial inflammation and AF pathogenesis is poorly understood. In this study, we demonstrate that activation of RhoA/ROCK1 signaling exacerbates atrial inflammation and remodeling, consequently increasing susceptibility to AF. Fasudil-mediated inhibition of RhoA/ROCK1 significantly attenuated atrial fibrosis, inflammation, and AF inducibility by suppressing the nuclear factor kappa-B p65 (NF-κBp65)/chemokine C-C-Motif ligand 2 (CCL2) signaling pathway. Restoring NF-κBp65 expression abolished these protective effects, establishing a causal relationship between RhoA/ROCK1 activation and NF-κB-mediated inflammation. Our results thus identify RhoA/ROCK1 as a critical mediator of pressure overload-induced AF and point to the RhoA/ROCK1-NF-κB/CCL2 axis as a promising therapeutic target for AF.