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

Heart failure (HF) affects over 26 million people worldwide, yet the pathologies of this complex syndrome have not been completely understood. Here, we investigated the involvement of deacetylase Sirtuin 1 (Sirt1) in HF and its downstream signaling pathways. A HF model was induced by the ligation of the left coronary artery in rats, where factors associated with left ventricular echocardiography, heart hemodynamics and ventricular mass indexes were recorded. Collagen volume fraction in heart tissues was determined by Masson's trichrome staining. Cell models of HF were also established (H2O2, 30 min) in cardiomyocytes harvested from suckling rats. HF rats presented with downregulated expressions of Sirt1, brain-derived neurotrophic factor (BDNF) and exhibited upregulated expressions of NF-kappa B p65 and miR-155. Repressed Sirt1 expression increased acetylation of NF-kappa B p65, resulting in the elevation of NF-KB p65 expression. NF-kappa B p65 silencing improved heart functions, decreased ventricular mass and reduced apoptosis in cardiomyocytes. MiR-155 inhibition upregulated its target gene BDNF, thereby reducing cardiomyocyte apoptosis. Sirt1 overexpression upregulated BDNF, improved heart function, and reduced apoptosis in cardiomyocytes. In conclusion, Sirt1 alleviates HF in rats through the NF-kappa B p65/miR-155/BDNF signaling cascade.

Automated summary

The findings suggest that Sirt1 plays a role in alleviating heart failure in rats through the NF-kappa B p65/miR-155/BDNF signaling cascade. Inhibition of Sirt1 increased acetylation of NF-kappa B p65, leading to elevated NF-KB p65 expression, while silencing NF-kappa B p65 improved heart functions and reduced cardiomyocyte apoptosis.