Knockdown of AMFR Alleviates Atrial Fibrosis in Atrial Fibrillation by Stabilizing SOD1 Protein Expression.

Abstract

PurposeDemonstration of the role of autocrine motility factor receptor (AMFR) in atrial fibrillation (AF) mice.MethodsThe AF model was established by administering Ang II to mice and transfected with AMFR knockdown or AMFR overexpression plasmids by tail vein injection of the AAV vector. Atrial fibrosis was examined by Masson staining. The mRNA expression of inflammatory factors TNF-α, IL-1β, and IL-6 in atrial tissue was detected by PCR. Reactive oxygen species (ROS) production in atrial tissue was examined by dihydroethidium staining. Apoptotic cells of atrial tissue were examined by TUNEL staining. The expression levels of fibrosis-related genes (COL1A1 and α-SMA), apoptosis-related genes (cleaved-caspase3 and cleaved-PARP), and SOD1 were detected by western blot. The ubiquitination level of superoxide dismutase 1 (SOD1) was detected by ubiquitination assay.ResultsAng II resulted in increased AMFR expression in mouse atrial tissue, and knockdown of AMFR inhibited atrial fibrosis, inflammatory factors, and ROS production, as well as apoptosis in mice. In addition, the knockdown of AMFR inhibited the ubiquitination level of SOD1 and increased the protein expression level of SOD1, whereas overexpression of AMFR exerted the opposite effect and aggravated Ang II-induced AF.ConclusionKnockdown of AMFR promotes SOD1 expression by inhibiting SOD1 ubiquitination levels and attenuates atrial fibrosis in AF mice by regulating SOD1.