Knockdown of HDAC9 attenuates sepsis-induced myocardial injury and inflammatory response.

Myocardial cell damage is associated with apoptosis and excessive inflammatory response in sepsis. Histone deacetylases (HDACs) are implicated in the progression of heart diseases. This study aims to explore the role of histone deacetylase 9 (HDAC9) in sepsis-induced myocardial injury. Lipopolysaccharide (LPS)-induced Sprague Dawley rats and cardiomyocyte line H9C2 were used as models in vivo and in vitro. The results showed that HDAC9 was significantly upregulated after LPS stimulation, and HDAC9 knockdown remarkably improved cardiac function, as evidenced by decreased LVEDD and LVESD, and increased FS% and EF%. In addition, HDAC9 silencing alleviated release of inflammatory cytokines (TNF-α, IL-6 and IL-1β) and cardiomyocyte apoptosis in vivo and in vitro. Furthermore, HDAC9 inhibition was proved to suppress NF-κB activation with reducing the levels of p-IκBα and p-p65, and p65 nuclear translocation. Additionally, interaction between miR-214-3p and HDAC9 was determined through bioinformatics analysis, RT-qPCR, western blot and dual luciferase reporter assay. Our data revealed that miR-214-3p directly targeted the 3'UTR of HDAC9. Our findings demonstrate that HDAC9 suppression ameliorates LPS-induced cardiac dysfunction by inhibiting the NF-κB signaling pathway and presents a promising therapeutic agent for the treatment of LPS-stimulated myocardial injury.