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BubR1 Insufficiency Recapitulates Changes Associated with Age-Related Cardiac Pathologies

ABSTRACT: Aging is a major risk factor for cardiovascular diseases, including heart failure, and contributes to pathological changes such as hypertrophy, fibrosis, and cellular senescence in the heart. BubR1, a critical regulator of the spindle assembly checkpoint, has been linked to various aging phenotypes, though its specific role in the heart remains largely unexplored. In this study, we examined the effects of BubR1 insufficiency in hypomorphic mice, revealing significant cardiac hypertrophy, fibrosis, and increased markers of cellular senescence. Transcriptomic analysis demonstrated that BubR1 insufficiency triggers molecular changes in the heart similar to those seen in aged hearts. Likewise, comparisons with end-stage heart failure patients showed that BubR1 deficiency mirrors transcriptomic alterations characteristic of heart failure. Importantly, our results indicate that heart failure is associated with reduced BubR1 levels, which also naturally declines with age in the heart. Our findings suggest that BubR1, traditionally known for its mitotic functions, plays a crucial role in maintaining the structure and function of the post-mitotic heart.

ORGANISM(S): Mus musculus

PROVIDER: GSE277997 | GEO | 2025/09/17

REPOSITORIES: GEO

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