HDAC5 inhibition attenuates ventricular remodeling and cardiac dysfunction
- Orphanet J Rare Dis. 2023 Sep 4;18(1):266. doi: 10.1186/s13023-023-02896-y.
- 1. Department of Cardiology, the Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, No. 306 Hualongqiao Road, Wenzhou, Zhejiang, 325000, China.
- 2. Department of Cardiology, the Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, No. 306 Hualongqiao Road, Wenzhou, Zhejiang, 325000, China. [email protected].
- # Contributed equally.
Background: This study aimed to investigate the role of histone deacetylase 5 (HDAC5) in ventricular remodeling and explore the therapeutic potential of the HDAC5 Inhibitor LMK235.
Methods: A transverse aortic constriction (TAC) mouse model and angiotensin II (Ang II)-treated H9C2 cells were used to evaluate the effects of HDAC5 inhibition with LMK235 on ventricular remodeling and cardiac dysfunction. Additionally, the involvement of the extracellular signal-regulated kinase (ERK)/early growth response protein 1 (EGR1) signaling pathway in regulating myocyte enhancer factor 2 A (MEF2A) expression was assessed.
Results: HDAC5 was upregulated in TAC mice and Ang II-treated H9C2 cells, suggesting its involvement in ventricular remodeling and cardiac dysfunction. LMK235 treatment significantly improved cardiac function in TAC mice and attenuated TAC-induced ventricular remodeling and Ang II-induced H9C2 cell hypertrophy. Mechanically, HDAC5 inhibition activated the ERK/EGR1 signaling pathway.
Conclusions: Our findings demonstrate that HDAC5 may suppress the activation of ERK/EGR1 signaling to regulate MEF2A expression and therefore participate in cardiac pathophysiology.