HDAC9 exacerbates myocardial infarction via inactivating Nrf2 pathways

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Epigenetics

Background:

• Myocardial infarction (MI) remains a primary global cause of mortality.
• Histone deacetylases (HDACs) are implicated in cardiovascular disease pathogenesis, including MI.
• The specific role of histone deacetylase 9 (HDAC9) in MI development requires elucidation.

Purpose of the Study:

• To investigate the function of HDAC9 in the context of myocardial infarction (MI).
• To explore the molecular mechanisms underlying HDAC9's involvement in heart disease progression.

Main Methods:

• Utilized in vivo and in vitro experimental models to assess HDAC9's impact on cardiac function.
• Quantified gene and protein expression using qRT-PCR and Western blotting.
• Analyzed cardiomyocyte proliferation, apoptosis, and differentiation via CCK-8, flow cytometry, and transwell assays.

Main Results:

• HDAC9 expression was found to be elevated in both in vivo and in vitro MI models.
• Reduced HDAC9 levels positively influenced cardiac function parameters, including LVEF, LVFS, LVEDD, and LVESD.
• HDAC9 knockdown promoted the activation of the Nrf2/Keap1/HO-1 signaling pathway.
• The HDAC9/Nrf2 axis was demonstrated to regulate cardiomyocyte proliferation, apoptosis, and myogenesis.

Conclusions:

• HDAC9 knockout confers cardioprotection against MI injury by activating the Nrf2 pathway.
• The HDAC9/Nrf2 axis represents a promising novel therapeutic target for myocardial infarction treatment.