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European Heart Rhythm Association established an expert consensus to define, characterize, and classify atrial cardiomyopathy into four subgroups based on their histopathological features. The predominant pathological feature of classes I and III is the hypertrophy of atrial cardiomyocytes. Here, we aim to investigate the mechanism of epigenetic transcriptional regulation of cardiomyocyte hypertrophy in atrial cardiomyopathy. Methods and Results. Compared with that of sinus rhythm control individuals, the myocardium of patients with atrial fibrillation exhibited increased levels of angiotensin II (AngII), chromatin-bound myocyte enhancer factor 2 (MEF2), acetylated histone H4 (H4ac), and H3K27ac; upregulation of hypertrophy-related genes; and decreased levels of histone deacetylase (HDAC) 4 and HDAC5 bound to the promoters of hypertrophy-related genes. Furthermore, incubation of atrial cardiomyocytes with AngII increased their cross-sectional area and improved the expression of hypertrophy-related genes. AngII also promoted the phosphorylation of HDAC4 and HDAC5 and induced their nuclear export. RNA sequencing analyses revealed that AngII significantly upregulated genes associated with cardiac hypertrophy. Chromatin immunoprecipitation showed that this correlated with increased levels of chromatin-bound MEF2, H4ac, and H3K27ac and decreased HDAC4 and HDAC5 enrichment in the promoters of hypertrophy-related genes. Moreover, these AngII-induced prohypertrophic effects could be partially reverted by treatment with the AngII receptor blocker losartan. Conclusions. AngII had a prohypertrophic effect on atrial cardiomyopathy which was epigenetic-dependent. Patients with atrial fibrillation manifest an increased susceptibility to hypertrophy and exhibit epigenetic characteristics that are permissive for the transcription of hypertrophy-related genes. AngII induces histone acetylation via the cytoplasmic-nuclear shuttling of HDACs, which constitutes a novel mechanism of atrial hypertrophy regulation and might provide a promising therapeutic strategy for atrial cardiomyopathy.<\/jats:p>","DOI":"10.1155\/2022\/6312100","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T22:05:06Z","timestamp":1655503506000},"page":"1-20","source":"Crossref","is-referenced-by-count":10,"title":["Angiotensin II Mediates Cardiomyocyte Hypertrophy in Atrial Cardiomyopathy via Epigenetic Transcriptional Regulation"],"prefix":"10.1155","volume":"2022","author":[{"given":"Liuying","family":"Zheng","sequence":"first","affiliation":[{"name":"Tianjin Medical University, Heping District, Tianjin 300070, China"},{"name":"Department of Cardiology, Tianjin Chest Hospital, Jinnan District, Tianjin 300222, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Wang","sequence":"additional","affiliation":[{"name":"Cardiac Surgery, Peking University First Hospital, Xicheng District, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Tianjin Chest Hospital, Jinnan District, Tianjin 300222, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Tianjin Chest Hospital, Jinnan District, Tianjin 300222, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Tianjin Chest Hospital, Jinnan District, Tianjin 300222, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Tianjin Chest Hospital, Jinnan District, Tianjin 300222, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0873-7229","authenticated-orcid":true,"given":"Xiaoyun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Tianjin Medical University, Heping District, Tianjin 300070, China"},{"name":"Department of Respiratory Critical Care Medicine and Sleep Center, Tianjin Chest Hospital, Tianjin 300222, China"},{"name":"Tianjin University, Tianjin 300072, China"},{"name":"Tianjin Tiangong University, Life Science School, Tianjin 300387, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Geng","sequence":"additional","affiliation":[{"name":"Shanxi Cardiovascular Hospital, 18 Yifen Street, Taiyuan, 030024 Shanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinping","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Fifth Central Hospital of Tianjin, Binhai Hospital of Peking University, Binhai New Area, Tianjin 300450, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5956-8579","authenticated-orcid":true,"given":"Yuecheng","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Tianjin Chest Hospital, Jinnan District, Tianjin 300222, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9288-7718","authenticated-orcid":true,"given":"Hongliang","family":"Cong","sequence":"additional","affiliation":[{"name":"Tianjin Medical University, Heping District, Tianjin 300070, China"},{"name":"Department of Cardiology, Tianjin Chest Hospital, Jinnan District, Tianjin 300222, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","article-title":"Exercitatio anatomica de motu cordis et sanguinis in animalibus","volume":"1628, article 17","author":"W. 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