MAPK14/AIFM2 pathway regulates mitophagy-dependent apoptosis to improve atrial fibrillation.

Abstract

OBJECTIVES: To investigate the role and mechanism of MAPK14/AIFM2 pathway in Ang II-induced atrial fibrillation in rats. METHODS: A rat model of AF was established for in vivo experiments and HL-1 cells were treated with Ang II to develop an in vitro model. In addition, HL1 cells overexpressing AIFM2 (oeAIFM2) were constructed. SB203580 was used to inhibit the expression of MAPK14. The role of MAPK14 in Ang II-AF model was investigated by in vivo electrophysiological examination and molecular biology tests. The role of MAPK14 / AIFM2 pathway on AF induced by Ang II was explored in vitro. RESULTS: MAPK14 and AIFM2 were significantly up-regulated in AF induced by Ang II (all P&#xa0;<&#xa0;0.05). In vivo experiments indicated that inhibition of MAPK14 down-regulated AIFM2, improved atrial electrical conduction, AF inducibility and durations, and alleviated the structural and functional damage of heart and mitochondria (all P&#xa0;<&#xa0;0.05). Both in vivo and in vitro tests showed that the MAPK14/AIFM2 pathway prevented Ang II-induced AF via regulating mitophagy-dependent apoptosis. CONCLUSIONS: Inhibition of the MAPK14/AIFM2 pathway improved Ang II-induced AF by inhibiting mitophagy-dependent apoptosis.