Combining increased Ca2+ influx, high-fat diet, and l-NAME produced a profound HFpEF phenotype in a mouse model, which was prevented by SAHA treatment.
Does SAHA treatment prevent the development of a severe HFpEF phenotype in a 3-Hit mouse model?
A novel '3-Hit' mouse model combining increased Ca2+ influx, high-fat diet, and l-NAME successfully induces a HFpEF phenotype that can be prevented by HDAC inhibition with SAHA.
Our study shows that three independent pathological stressors (increased Ca 2+ influx, high-fat diet, and l-NAME) together produce a profound HFpEF phenotype. The primary mechanisms include HDAC-dependent-CM hypertrophy, necrosis, increased M 2 -macrophage population, fibroblast activation, and myocardial fibrosis. A role for HDAC activation in the HFpEF phenotype was shown in studies with SAHA treatment, which prevented the severe HFpEF phenotype. This “3-Hit” mouse model could be helpful in identifying novel therapeutic strategies to treat HFpEF.
Li et al. (Fri,) conducted a other in Heart failure with preserved ejection fraction (HFpEF). Three independent pathological stressors (increased Ca2+ influx, high-fat diet, and l-NAME) and SAHA treatment was evaluated on HFpEF phenotype. Combining increased Ca2+ influx, high-fat diet, and l-NAME produced a profound HFpEF phenotype in a mouse model, which was prevented by SAHA treatment.