Our previous investigation indicated that angiotensin II (Ang II) enhances the expression of Kv1.5, a promising target for the treatment of atrial fibrillation (AF), by activating reactive oxygen species (ROS)-dependent phosphorylation of Smad 2/3 (forming P-Smad 2/3) and ERK 1/2 (forming P-ERK 1/2).
In the cultured embryonic cortical neurons, the treatment of control (CTL) rat-derived AF significantly increased the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2)-mediated signaling that is essential for fetal neurodevelopment.
In conclusion, our study indicates that H<sub>2</sub>S downregulates Ang II-induced atrial Kv1.5 expression by attenuating Nox4-related ROS-triggered P-Smad2/3 and P-ERK 1/2 activation during AF.
An ACE-dependent increase in the amounts of activated Erk1/Erk2 in atrial interstitial cells may contribute as a molecular mechanism for the development of atrial fibrosis in patients with AF.