Cardiac-specific BACH1 ablation attenuates pathological cardiac hypertrophy by inhibiting the Ang II type 1 receptor expression and the Ca2+/CaMKII pathway.

Transcription factor BACH1 is increased in failing human myocardium and hypertrophic human hearts. We revealed that cardiomyocyte-specific BACH1 ablation in mice protected the hearts against Ang II- and pressure overload-induced cardiac hypertrophy and fibrosis, and preserved cardiac function. BACH1 activated AT1R promoter activity under Ang II stimulation, and BACH1-mediated facilitation of cardiac hypertrophy under Ang II stimulation was regulated at least in part by AT1R expression. Moreover, BACH1 silencing attenuated the norepinephrine-stimulated CaMKII signaling pathway and hypertrophic growth of cardiomyocytes. Our findings suggest that BACH1 may pose a promising therapeutic target in pathological cardiac hypertrophy and heart failure.