Sirt1 improves heart failure through modulating the NF-κB p65/microRNA-155/BNDF signaling cascade

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Biochemistry

Background:

• Heart failure (HF) is a complex syndrome affecting millions globally, with incompletely understood pathological mechanisms.
• Deacetylase Sirtuin 1 (Sirt1) is implicated in various cellular processes, but its role in HF requires further elucidation.

Purpose of the Study:

• To investigate the role of Sirtuin 1 (Sirt1) in the pathogenesis of heart failure (HF).
• To identify downstream signaling pathways regulated by Sirt1 in HF models.

Main Methods:

• Established rat models of HF via left coronary artery ligation and in vitro cardiomyocyte models using H2O2.
• Assessed left ventricular echocardiography, hemodynamics, ventricular mass, and collagen deposition.
• Quantified protein and microRNA expression, including Sirt1, BDNF, NF-κB p65, and miR-155.

Main Results:

• HF rats exhibited decreased Sirt1 and BDNF, with increased NF-κB p65 and miR-155.
• Reduced Sirt1 expression led to increased NF-κB p65 acetylation and expression, worsening cardiac function.
• NF-κB p65 silencing and miR-155 inhibition improved cardiac function and reduced cardiomyocyte apoptosis.
• Sirt1 overexpression upregulated BDNF, enhancing cardiac function and reducing apoptosis.

Conclusions:

• Sirtuin 1 (Sirt1) plays a protective role in heart failure (HF) by modulating the NF-κB p65/miR-155/BDNF signaling cascade.
• Targeting the Sirt1 pathway offers a potential therapeutic strategy for mitigating HF progression and improving cardiac outcomes.