HDAC5 inhibition attenuates ventricular remodeling and cardiac dysfunction
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-023-02896-y |
| _version_ | 1797556536395956224 |
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| author | Chenxi Zhu Zhehao Piao Li Jin |
| author_facet | Chenxi Zhu Zhehao Piao Li Jin |
| author_sort | Chenxi Zhu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-10T17:03:18Z |
| format | Article |
| id | doaj.art-cf1e580085694ba49c8ea65b3edf1939 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-03-10T17:03:18Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-cf1e580085694ba49c8ea65b3edf19392023-11-20T10:53:40ZengBMCOrphanet Journal of Rare Diseases1750-11722023-09-0118111310.1186/s13023-023-02896-yHDAC5 inhibition attenuates ventricular remodeling and cardiac dysfunctionChenxi Zhu0Zhehao Piao1Li Jin2Department of Cardiology, the Second Affiliated Hospital, Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Cardiology, the Second Affiliated Hospital, Yuying Children’s Hospital of Wenzhou Medical UniversityDepartment of Cardiology, the Second Affiliated Hospital, Yuying Children’s Hospital of Wenzhou Medical UniversityAbstract 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.https://doi.org/10.1186/s13023-023-02896-yHDAC5Cardiac hypertrophyEGR1MEF2ATherapies |
| spellingShingle | Chenxi Zhu Zhehao Piao Li Jin HDAC5 inhibition attenuates ventricular remodeling and cardiac dysfunction Orphanet Journal of Rare Diseases HDAC5 Cardiac hypertrophy EGR1 MEF2A Therapies |
| title | HDAC5 inhibition attenuates ventricular remodeling and cardiac dysfunction |
| title_full | HDAC5 inhibition attenuates ventricular remodeling and cardiac dysfunction |
| title_fullStr | HDAC5 inhibition attenuates ventricular remodeling and cardiac dysfunction |
| title_full_unstemmed | HDAC5 inhibition attenuates ventricular remodeling and cardiac dysfunction |
| title_short | HDAC5 inhibition attenuates ventricular remodeling and cardiac dysfunction |
| title_sort | hdac5 inhibition attenuates ventricular remodeling and cardiac dysfunction |
| topic | HDAC5 Cardiac hypertrophy EGR1 MEF2A Therapies |
| url | https://doi.org/10.1186/s13023-023-02896-y |
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