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Administration of USP7 inhibitor p22077 alleviates Angiotensin II (Ang II)-induced atrial fibrillation in Mice.
- Source :
-
Hypertension research : official journal of the Japanese Society of Hypertension [Hypertens Res] 2024 May; Vol. 47 (5), pp. 1309-1322. Date of Electronic Publication: 2024 Feb 19. - Publication Year :
- 2024
-
Abstract
- Atrial fibrillation (AF), the most common cardiac arrhythmia, is an important contributor to mortality and morbidity. Ubquitin-specific protease 7 (USP7), one of the most abundant ubiquitin-specific proteases (USP), participated in many cellular events, such as cell proliferation, apoptosis, and tumourigenesis. However, its role in AF remains unknown. Here, the mice were treated with Ang II infusion to induce the AF model. Echocardiography was used to measure the atrial diameter. Electrical stimulation was programmed to measure the induction and duration of AF. The changes in atrial remodeling were measured using routine histologic analysis. Here, a significant increase in USP7 expression was observed in Ang II-stimulated atrial cardiomyocytes and atrial tissues, as well as in atrial tissues from patients with AF. The administration of p22077, the inhibitor of USP7, attenuated Ang II-induced inducibility and duration of AF, atrial dilatation, connexin dysfunction, atrial fibrosis, atrial inflammation, and atrial oxidase stress, and then inhibited the progression of AF. Mechanistically, the administration of p22077 alleviated Ang II-induced activation of TGF-β/Smad2, NF-κB/NLRP3, NADPH oxidases (NOX2 and NOX4) signals, the up-regulation of CX43, ox-CaMKII, CaMKII, Kir2.1, and down-regulation of SERCA2a. Together, this study, for the first time, suggests that USP7 is a critical driver of AF and revealing USP7 may present a new target for atrial fibrillation therapeutic strategies.<br /> (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)
- Subjects :
- Animals
Mice
Male
Mice, Inbred C57BL
Heart Atria drug effects
Heart Atria metabolism
Heart Atria pathology
Myocytes, Cardiac drug effects
Myocytes, Cardiac metabolism
Humans
Atrial Remodeling drug effects
Atrial Fibrillation metabolism
Atrial Fibrillation chemically induced
Atrial Fibrillation drug therapy
Atrial Fibrillation prevention & control
Angiotensin II
Ubiquitin-Specific Peptidase 7 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1348-4214
- Volume :
- 47
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Hypertension research : official journal of the Japanese Society of Hypertension
- Publication Type :
- Academic Journal
- Accession number :
- 38374239
- Full Text :
- https://doi.org/10.1038/s41440-024-01581-2