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

TL;DR

This study shows that asymmetric dimethylarginine (ADMA) increases oxidative stress and promotes atrial remodeling in heart cells, potentially contributing to atrial fibrillation.

Contribution

The study reveals a novel mechanism by which ADMA induces oxidative stress and TGF-β1 expression in atrial cells, linking it to atrial remodeling in atrial fibrillation.

Findings

ADMA increased ROS generation and TGF-β1 expression in HL-1 cells, which was reversed by NAC.

AF patients had higher serum ADMA and TGF-β1 levels and lower NO levels compared to controls.

Abstract

Atrial fibrillation (AF) is a common cardiac arrhythmia, and endothelial dysfunction and oxidative stress (OS) are key mechanisms promoting atrial remodeling. Asymmetric dimethylarginine (ADMA) inhibits nitric oxide synthase (NOS) but its role in AF-related atrial remodeling remains unclear.

Mouse atrial myocyte HL-1 cells were treated with ADMA, H2O2, N-acetylcysteine (NAC), or their combinations. Cell viability, reactive oxygen species (ROS) levels, and TGF-β1 expression were detected using CCK-8, flow cytometry, fluorescence microscopy, and Western blot. A clinical cohort study included 60 AF patients and 30 controls to measure serum ADMA, TGF-β1, and NO levels.

ADMA (30 μM) significantly increased ROS generation and upregulated p47phox and TGF-β1 expression in HL-1 cells, which was reversed by NAC. AF patients had higher serum ADMA and TGF-β1 levels and lower NO levels than controls (P<0.01).

ADMA may induce TGF-β1 expression by enhancing NOX-ROS levels, leading to myocardial oxidative damage and atrial remodeling, which provides new insights into AF pathophysiology.

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