Signal Recognition Granule Receptor Beta Subunit Promotes Arrhythmogenic Remodeling in the Heart Failure Mice
Jingjing Zhang1,2,3, Yucheng Pan1,2,3, Yang Gong1,2,3
1Department of Cardiology Renmin Hospital of Wuhan University Wuhan Hubei People's Republic of China.
Journal of the American Heart Association
|January 22, 2026
Summary
Reducing signal recognition particle receptor beta subunit (Srprb) improved heart failure outcomes in mice by decreasing ventricular arrhythmias. Conversely, increasing Srprb worsened heart failure and increased arrhythmias, highlighting Srprb as a therapeutic target.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Endoplasmic Reticulum Stress
Background:
- Heart failure (HF) is a leading cause of death globally, frequently complicated by ventricular arrhythmias (VAs).
- Signal recognition particle receptor beta subunit (Srprb) is an endoplasmic reticulum protein implicated in protein processing.
Purpose of the Study:
- To investigate the role of Srprb in cardiac remodeling and VA susceptibility in a mouse model of heart failure.
Main Methods:
- Cardiac-specific Srprb overexpression or knockdown was achieved using adeno-associated viruses in mice.
- A pressure overload-induced heart failure model was created via aortic banding.
- Cardiac function, electrophysiology, and molecular changes were assessed, alongside in vitro studies on cardiomyocytes and fibroblasts.
Main Results:
- Srprb knockdown ameliorated cardiac structural and electrical remodeling, reducing VAs in pressure-overload induced heart failure.
- Srprb overexpression exacerbated remodeling and increased VA incidence.
- In vitro, Srprb modulation affected cardiomyocyte hypertrophy and fibroblast fibrosis, mediated by endoplasmic reticulum stress and the TLR4/CaMKII/NF-κB pathway.
Conclusions:
- Srprb knockdown confers protection against ventricular remodeling and arrhythmias in heart failure.
- Srprb overexpression exacerbates heart failure phenotypes and increases VA risk.
- Targeting Srprb may offer a novel therapeutic strategy for managing heart failure complications.
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