HDAC9 exacerbates myocardial infarction via inactivating Nrf2 pathways.

Objectives Myocardial infarction (MI) is the leading cause of death worldwide. Histone deacetylases (HDACs) collectively participate in the initiation and progression of heart diseases, including MI. This study aimed to investigate the roles of histone deacetylase 9 (HDAC9) in the development of MI. Methods In vivo and in vitro assays were conducted to determine the effects of HDAC9 on heart function and MI. qRT-PCR was applied to determine the mRNA level. Western blot was performed for protein expression. Immunofluorescence was applied to detect the fluorescence tensity of Myog and Myod. CCK-8, flow cytometry and transwell assays were carried out for function analysis. Key findings HDAC9 was upregulated in MI models in vivo and in vitro. Downregulated HDAC9 modulated the changes in left ventricle ejection fraction (LVEF), left ventricle fractional shortening (LVFS) and left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD). Moreover, HDAC9 knockdown activated NFE2-related factor 2 (Nrf2)/Keap1/HO-1 pathways. Additionally, HDAC9/Nrf2 axis modulated the proliferation, apoptosis and myogenesis of cardiomyocytes. Conclusions Taken together, HDAC9 knockout induced the activation of Nrf2 and protected heart from MI injury. Thus, the HDAC9/Nrf2 axis can be a novel marker for the treatment of MI.