USP38 Exacerbates Atrial Inflammation, Fibrosis, and Susceptibility to Atrial Fibrillation After Myocardial Infarction in Mice

Authors

Yang Gong
Tingting Yu
Wei Shuai
Tao Chen
Jingjing Zhang
He Huang

Publication Date

11-12-2023

Journal

Molecular Medicine

Abstract

BACKGROUND: Inflammation plays an important role in the pathogenesis of atrial fibrillation (AF) after myocardial infarction (MI). The role of USP38, a member of the ubiquitin-specific protease family, on MI-induced atrial inflammation, fibrosis, and associated AF is unclear.

METHODS: In this study, we surgically constructed a mouse MI model using USP38 cardiac conditional knockout (USP38-CKO) and cardiac-specific overexpression (USP38-TG) mice and applied biochemical, histological, electrophysiological characterization and molecular biology to investigate the effects of USP38 on atrial inflammation, fibrosis, and AF and its mechanisms.

RESULTS: Our results revealed that USP38-CKO attenuates atrial inflammation, thereby ameliorating fibrosis, and abnormal electrophysiologic properties, and reducing susceptibility to AF on day 7 after MI. USP38-TG showed the opposite effect. Mechanistically, The TAK1/NF-κB signaling pathway in the atria was significantly activated after MI, and phosphorylated TAK1, P65, and IκBα protein expression was significantly upregulated. USP38-CKO inhibited the activation of the TAK1/NF-κB signaling pathway, whereas USP38-TG overactivated the TAK1/NF-κB signaling pathway after MI. USP38 is dependent on the TAK1/NF-κB signaling pathway and regulates atrial inflammation, fibrosis, and arrhythmias after MI to some extent.

CONCLUSIONS: USP38 plays an important role in atrial inflammation, fibrosis, and AF susceptibility after MI, providing a promising target for the treatment of AF after MI.

Keywords

Atrial fibrillation, Inflammation, Myocardial infarction, Ubiquitin-specific protease

Comments

Supplementary Materials

PMID: 37953295