Asymmetric dimethylarginine mediates oxidative stress and atrial remodeling in HL-1 cells

Chengyun Yu¹Ming Zhang²Xuepin Chen³Wei Xia^4*

• ¹Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
• ²Shandong Second Medical University, Weifang, China
• ³Qingdao Central Hospital of University of Health and Rehabilitation Sciences, Qingdao, China
• ⁴Qingdao Hospital, University of Health and Rehabilitation Sciences（Qingdao Municipal Hospital）, Qingdao, China

Endothelial dysfunction and oxidative stress (OS) are significant mechanisms that promote atrial remodeling, ultimately leading to atrial fibrillation (AF). Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), reduces nitric oxide synthesis and contributes to endothelial dysfunction. However, the specific role of ADMA and its relationship with atrial remodeling in AF remain poorly understood. In this study, mouse atrial myocyte HL-1 cells were utilized as the model and treated with varying concentrations of ADMA, H2O2, N-acetylcysteine (NAC), or their combinations. Treatment with ADMA (30 μM) significantly increased the generation of reactive oxygen species (ROS) and elevated the expression of p47phox and TGF-β1, however, these effects were reversed by the reactive oxygen species scavenger NAC. The cohort study (60 AF patients, 30 controls) showed elevated ADMA, TGF-β1 and reduced NO in AF patients (P<0.01). The findings suggest that ADMA likely induces TGF-β1 expression mechanistically by enhancing NOX-ROS levels, which subsequently leads to myocardial oxidative damage and atrial remodeling.