YAK577 treatment significantly restored isoproterenol-induced reductions in left ventricular fractional shortening and ejection fraction and ameliorated cardiac fibrosis in a mouse model of heart failure.
Does YAK577 attenuate cardiac remodeling and fibrosis in an isoproterenol-induced heart failure mouse model?
The novel HDAC inhibitor YAK577 attenuates cardiac remodeling and fibrosis in a mouse model of heart failure via the HDAC8/MMP12 pathway.
p-value: p=<0.001
BACKGROUND AND OBJECTIVES: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. METHODS: New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area. The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). RESULTS: mRNA levels, while HDAC8 knockdown downregulated these genes. CONCLUSIONS: YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.
Zhou et al. (Mon,) conducted a other in Isoproterenol-induced heart failure (n=30). YAK577 vs. Isoproterenol alone was evaluated on Left ventricular fractional shortening and ejection fraction (p=<0.001). YAK577 treatment significantly restored isoproterenol-induced reductions in left ventricular fractional shortening and ejection fraction and ameliorated cardiac fibrosis in a mouse model of heart failure.