A reduced TBX5-dependent gene regulatory network links atrial fibrillation and heart failure - PubMed
3 hours ago
- #Heart Failure
- #Atrial Fibrillation
- #Gene Regulatory Network
- Atrial fibrillation (AF) and heart failure (HF) often coexist and worsen each other's outcomes.
- Shared molecular mechanisms were investigated using mouse Tbx5 conditional knockout (Tbx5 cKO) AF model and transverse aortic constriction (TAC) HF model.
- Highly correlated changes in atrial transcriptional and genomic profiles were observed, including downregulated atrial Tbx5 expression in both mouse and human HF.
- Over 100 transcription factor genes were coordinately dysregulated in the atria of Tbx5 cKO and TAC models.
- The wild-type atrial TBX5-driven gene regulatory network (GRN), including Klf15 (a repressor of cardiomyocyte hypertrophy), was disrupted in both models.
- A disease-specific network featuring Sox9 emerged in activated fibroblasts of Tbx5 cKO and TAC models.
- Results suggest a shared genomic injury response may underlie the reciprocal risk between AF and HF.