HDAC5 inhibition attenuates ventricular remodeling and cardiac dysfunction
Chenxi Zhu1, Zhehao Piao1, Li Jin2
1Department of Cardiology, the Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, No. 306 Hualongqiao Road, Wenzhou, Zhejiang, 325000, China.
Orphanet Journal of Rare Diseases
|September 4, 2023
Summary
Histone deacetylase 5 (HDAC5) plays a role in cardiac dysfunction. Inhibiting HDAC5 with LMK235 improved heart function and reduced ventricular remodeling by activating ERK/EGR1 signaling.
Area of Science:
- Cardiology
- Molecular Biology
- Pharmacology
Background:
- Ventricular remodeling and cardiac dysfunction are significant health concerns.
- Histone deacetylase 5 (HDAC5) is implicated in the pathophysiology of cardiac diseases.
Purpose of the Study:
- To investigate the role of HDAC5 in ventricular remodeling.
- To explore the therapeutic potential of the HDAC5 inhibitor LMK235 for cardiac dysfunction.
Main Methods:
- Utilized a transverse aortic constriction (TAC) mouse model and angiotensin II (Ang II)-treated H9C2 cells.
- Assessed the effects of LMK235 on cardiac function, ventricular remodeling, and cellular hypertrophy.
- Examined the involvement of the extracellular signal-regulated kinase (ERK)/early growth response protein 1 (EGR1) signaling pathway.
Main Results:
- HDAC5 expression was upregulated in TAC mice and Ang II-treated H9C2 cells.
- LMK235 treatment improved cardiac function in TAC mice and attenuated ventricular remodeling and hypertrophy.
- HDAC5 inhibition activated the ERK/EGR1 signaling pathway.
Conclusions:
- HDAC5 may suppress ERK/EGR1 signaling, influencing myocyte enhancer factor 2A (MEF2A) expression.
- HDAC5 inhibition presents a potential therapeutic strategy for cardiac pathophysiology.
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