| First Author | Xiao Z | Year | 2023 |
| Journal | Europace | Volume | 26 |
| Issue | 1 | PubMed ID | 38288617 |
| Mgi Jnum | J:360425 | Mgi Id | MGI:7730999 |
| Doi | 10.1093/europace/euad366 | Citation | Xiao Z, et al. (2023) Ubiquitin-specific protease 38 promotes inflammatory atrial fibrillation induced by pressure overload. Europace 26(1) |
| abstractText | AIMS: Atrial structural and electrical remodelling is a major reason for the initiation and perpetuation of atrial fibrillation (AF). Ubiquitin-specific protease 38 (USP38) is a deubiquitinating enzyme, but its function in the heart remains unknown. The aim of this study was to investigate the effect of USP38 in pressure overload-induced AF. METHODS AND RESULTS: Cardiac-specific knockout USP38 and cardiac-specific transgenic USP38 mice and their corresponding control mice were used in this study. After 4 weeks with or without aortic banding (AB) surgery, atrial echocardiography, atrial histology, electrophysiological study, and molecular analysis were assessed. Ubiquitin-specific protease 38 knockout mice showed a remarkable improvement in vulnerability to AF, atrial weight and diameter, atrial fibrosis, and calcium-handling protein expression after AB surgery. Conversely, USP38 overexpression further increased susceptibility to AF by exacerbating atrial structural and electrical remodelling. Mechanistically, USP38 interacted with and deubiquitinated nuclear factor-kappa B (NF-kappaB), and USP38 overexpression increased the level of p-NF-kappaB in vivo and in vitro, accompanied by the upregulation of NOD-like receptor protein 3 (NLRP3) and inflammatory cytokines, suggesting that USP38 contributes to adverse effects by driving NF-kappaB/NLRP3-mediated inflammatory responses. CONCLUSION: Overall, our study indicates that USP38 promotes pressure overload-induced AF through targeting NF-kappaB/NLRP3-mediated inflammatory responses. |
