Mechanism of histone deacetylases in cardiac hypertrophy and its therapeutic inhibitors
Cardiac hypertrophy is a key process in cardiac remodeling development, leading to ventricle enlargement and heart failure. Recently, studies show the complicated relation between cardiac hypertrophy and epigenetic modification. Post-translational modification of histone is an essential part of epig...
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.931475/full |
| _version_ | 1818002331260682240 |
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| author | Yu Han Yu Han Jiali Nie Jiali Nie Dao Wen Wang Dao Wen Wang Li Ni Li Ni |
| author_facet | Yu Han Yu Han Jiali Nie Jiali Nie Dao Wen Wang Dao Wen Wang Li Ni Li Ni |
| author_sort | Yu Han |
| collection | DOAJ |
| description | Cardiac hypertrophy is a key process in cardiac remodeling development, leading to ventricle enlargement and heart failure. Recently, studies show the complicated relation between cardiac hypertrophy and epigenetic modification. Post-translational modification of histone is an essential part of epigenetic modification, which is relevant to multiple cardiac diseases, especially in cardiac hypertrophy. There is a group of enzymes related in the balance of histone acetylation/deacetylation, which is defined as histone acetyltransferase (HAT) and histone deacetylase (HDAC). In this review, we introduce an important enzyme family HDAC, a key regulator in histone deacetylation. In cardiac hypertrophy HDAC I downregulates the anti-hypertrophy gene expression, including Kruppel-like factor 4 (Klf4) and inositol-5 phosphatase f (Inpp5f), and promote the development of cardiac hypertrophy. On the contrary, HDAC II binds to myocyte-specific enhancer factor 2 (MEF2), inhibit the assemble ability to HAT and protect against cardiac hypertrophy. Under adverse stimuli such as pressure overload and calcineurin stimulation, the HDAC II transfer to cytoplasm, and MEF2 can bind to nuclear factor of activated T cells (NFAT) or GATA binding protein 4 (GATA4), mediating inappropriate gene expression. HDAC III, also known as SIRTs, can interact not only to transcription factors, but also exist interaction mechanisms to other HDACs, such as HDAC IIa. We also present the latest progress of HDAC inhibitors (HDACi), as a potential treatment target in cardiac hypertrophy. |
| first_indexed | 2024-04-14T03:44:35Z |
| format | Article |
| id | doaj.art-d4555c1efe074115ae6e54f23f37d5c5 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-14T03:44:35Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-d4555c1efe074115ae6e54f23f37d5c52022-12-22T02:14:21ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-07-01910.3389/fcvm.2022.931475931475Mechanism of histone deacetylases in cardiac hypertrophy and its therapeutic inhibitorsYu Han0Yu Han1Jiali Nie2Jiali Nie3Dao Wen Wang4Dao Wen Wang5Li Ni6Li Ni7Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, ChinaDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, ChinaDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, ChinaDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, ChinaCardiac hypertrophy is a key process in cardiac remodeling development, leading to ventricle enlargement and heart failure. Recently, studies show the complicated relation between cardiac hypertrophy and epigenetic modification. Post-translational modification of histone is an essential part of epigenetic modification, which is relevant to multiple cardiac diseases, especially in cardiac hypertrophy. There is a group of enzymes related in the balance of histone acetylation/deacetylation, which is defined as histone acetyltransferase (HAT) and histone deacetylase (HDAC). In this review, we introduce an important enzyme family HDAC, a key regulator in histone deacetylation. In cardiac hypertrophy HDAC I downregulates the anti-hypertrophy gene expression, including Kruppel-like factor 4 (Klf4) and inositol-5 phosphatase f (Inpp5f), and promote the development of cardiac hypertrophy. On the contrary, HDAC II binds to myocyte-specific enhancer factor 2 (MEF2), inhibit the assemble ability to HAT and protect against cardiac hypertrophy. Under adverse stimuli such as pressure overload and calcineurin stimulation, the HDAC II transfer to cytoplasm, and MEF2 can bind to nuclear factor of activated T cells (NFAT) or GATA binding protein 4 (GATA4), mediating inappropriate gene expression. HDAC III, also known as SIRTs, can interact not only to transcription factors, but also exist interaction mechanisms to other HDACs, such as HDAC IIa. We also present the latest progress of HDAC inhibitors (HDACi), as a potential treatment target in cardiac hypertrophy.https://www.frontiersin.org/articles/10.3389/fcvm.2022.931475/fullcardiac hypertrophyepigeneticshistone deacetylasegene regulationsmall molecule inhibitors |
| spellingShingle | Yu Han Yu Han Jiali Nie Jiali Nie Dao Wen Wang Dao Wen Wang Li Ni Li Ni Mechanism of histone deacetylases in cardiac hypertrophy and its therapeutic inhibitors Frontiers in Cardiovascular Medicine cardiac hypertrophy epigenetics histone deacetylase gene regulation small molecule inhibitors |
| title | Mechanism of histone deacetylases in cardiac hypertrophy and its therapeutic inhibitors |
| title_full | Mechanism of histone deacetylases in cardiac hypertrophy and its therapeutic inhibitors |
| title_fullStr | Mechanism of histone deacetylases in cardiac hypertrophy and its therapeutic inhibitors |
| title_full_unstemmed | Mechanism of histone deacetylases in cardiac hypertrophy and its therapeutic inhibitors |
| title_short | Mechanism of histone deacetylases in cardiac hypertrophy and its therapeutic inhibitors |
| title_sort | mechanism of histone deacetylases in cardiac hypertrophy and its therapeutic inhibitors |
| topic | cardiac hypertrophy epigenetics histone deacetylase gene regulation small molecule inhibitors |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.931475/full |
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