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

Abstract

Inflammation is a common cause of cardiac arrhythmia. Angiotensin II (Ang II) 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 II on inflammatory mechanisms and oxidative stress using HL-1 atrial myocytes. We showed that Ang II activated c-Jun N-terminal kinase (JNK) phosphorylation and other inflammatory markers, such as transforming growth factor-beta 1 (TGF-beta 1) and tumor necrosis factor-alpha (TNF-alpha). Ang II decreased oxygen consumption rate, which resulted in reactive oxygen species (ROS) generation and inhibition of ROS blocked Ang II-mediated JNK phosphorylation and TGF-beta 1 induction. Ang II induced the expression of its specific receptor, AT1R. Ang II-induced intracellular calcium production associated with Ang II-mediated signalling pathways. In addition, the generated ROS and calcium stimulated AMPK phosphorylation. Inhibiting AMPK blocked Ang II-mediated JNK and TGF-beta signalling pathways. Ang II concentration, along with TGF-beta 1 and tumor necrosis factor-alpha levels, was slightly increased in plasma of patients with atrial fibrillation. Taken together, these results suggest that Ang II 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.