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

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

  • Cell Signal. 2026 Feb:138:112275. doi: 10.1016/j.cellsig.2025.112275.
Mingzhi Wan 1,  Yao Li 2,  Nana Qin 3,  Zijun Zhou 4,  Boxuan Sun 4,  Bo Xing 5,  Yiwen Wang 2,  Jinfeng Duan 1,  Yuting Huang 4,  Liming Yu 6,  Huishan Wang 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, 83 Wenhua Road, Shenyang, Liaoning 110016, China; China Medical University, Shenyang, Liaoning 110122, China.
  • 2 State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, 83 Wenhua Road, Shenyang, Liaoning 110016, China; Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning 110819, China.
  • 3 State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, 83 Wenhua Road, Shenyang, Liaoning 110016, China; Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, China.
  • 4 State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, 83 Wenhua Road, Shenyang, Liaoning 110016, China.
  • 5 State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, 83 Wenhua Road, Shenyang, Liaoning 110016, China; Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
  • 6 State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, 83 Wenhua Road, Shenyang, Liaoning 110016, China. Electronic address: [email protected].
  • 7 State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, 83 Wenhua Road, Shenyang, Liaoning 110016, China. Electronic address: [email protected].
PMID: 41317932 DOI: 10.1016/j.cellsig.2025.112275
Abstract

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.

Keywords

Atrial fibrillation; Atrial inflammation; Atrial remodeling; Ras homolog gene family member a; Rho-associated kinase 1.

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