Angiotensin II affects inflammation mechanisms via AMPK-related signalling pathways in HL-1 atrial myocytes.

Inflammation is a common cause of cardiac arrhythmia. Angiotensin ІІ (Ang ІІ) is a major contributing factor in the pathogenesis of cardiac inflammation; however, its underlying molecular mechanism remains unclear. Here, we explored the effect of Ang ІІ on inflammatory mechanisms and oxidative stress using HL-1 atrial myocytes. We showed that Ang ІІ activated c-Jun N-terminal kinase (JNK) phosphorylation and other inflammatory markers, such as transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α). Ang ІІ decreased oxygen consumption rate, which resulted in reactive oxygen species (ROS) generation and inhibition of ROS blocked Ang II-mediated JNK phosphorylation and TGF-β1 induction. Ang ІІ induced the expression of its specific receptor, AT1R. Ang II-induced intracellular calcium production associated with Ang ІІ-mediated signalling pathways. In addition, the generated ROS and calcium stimulated AMPK phosphorylation. Inhibiting AMPK blocked Ang II-mediated JNK and TGF-β signalling pathways. Ang ІІ concentration, along with TGF-β1 and tumor necrosis factor-α levels, was slightly increased in plasma of patients with atrial fibrillation. Taken together, these results suggest that Ang ІІ induces inflammation mechanisms through an AMPK-related signalling pathway. Our results provide new molecular targets for the development of therapeutics for inflammation-related conditions, such as atrial fibrillation.