LncRNA Foxo6os as a Novel " Scaffold" Mediates MYBPC3 in Combating Pathological Cardiac Hypertrophy and Heart Failure

Area of Science:

• Molecular Biology
• Cardiology
• Genetics

Background:

• Heart failure (HF) is a critical stage of cardiac disease with unclear molecular drivers.
• Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in cardiac hypertrophy and HF progression.

Purpose of the Study:

• To investigate the role of the lncRNA forkhead box O6, opposite strand (Foxo6os) in the development of HF.
• To elucidate the molecular mechanisms by which Foxo6os influences cardiac function.

Main Methods:

• Utilized a murine model of HF induced by transverse aortic constriction (TAC).
• Assessed the impact of Foxo6os knockdown and overexpression on cardiomyocyte hypertrophy and cardiac function.
• Investigated the interaction between Foxo6os, myosin-binding protein-C (MYBPC3), and protein kinase C alpha (PKC-α).

Main Results:

• Foxo6os was significantly downregulated in the TAC-induced HF model.
• Foxo6os knockdown exacerbated cardiomyocyte hypertrophy, indicated by increased ANP, BNP, and MYH7 expression.
• Foxo6os overexpression improved cardiac function and reduced adverse cardiac remodeling.
• Foxo6os directly interacts with MYBPC3, promoting its phosphorylation by PKC-α, which is crucial for maintaining myocardial contractility.

Conclusions:

• Foxo6os plays a protective role in preserving cardiomyocyte contractile function.
• The findings highlight Foxo6os as a potential novel therapeutic target for mitigating HF progression.