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Chidamide (HBI\u20108000) is a domestically produced benzamide\u2010based histone deacetylase isoform\u2010selective inhibitor used for the treatment of relapsed refractory peripheral T\u2010cell lymphomas. Based on our in\u00a0vivo studies, we propose that HBI\u20108000 exerts its therapeutic effects by inhibiting myocardial fibrosis and myocardial hypertrophy in HFpEF patients. At the cellular level, we found that HBI\u20108000 inhibits AngII\u2010induced proliferation and activation of CFs and downregulates the expression of fibrosis\u2010related factors. In addition, we observed that the HFpEF group and AngII stimulation significantly increased the expression of TGF\u2010\u03b21 as well as phosphorylated p38MAPK, JNK and ERK, whereas the expression of the above factors was significantly reduced after HBI\u20108000 treatment. Activation of the TGF\u2010\u03b21\/MAPK pathway promotes the development of fibrotic remodelling, and pretreatment with SB203580 (p38MAPK inhibitor) reverses this pathological change. In conclusion, our data suggest that HBI\u20108000 inhibits fibrosis by modulating the TGF\u2010\u03b21\/MAPK pathway thereby improving HFpEF. Therefore, HBI\u20108000 may become a new hope for the treatment of HFpEF patients.<\/jats:p>","DOI":"10.1111\/jcmm.18238","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T02:45:41Z","timestamp":1710989141000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<scp>HBI<\/scp>\u20108000 improves heart failure with preserved ejection fraction via the <scp>TGF\u2010\u03b21<\/scp>\/<scp>MAPK<\/scp> signalling pathway"],"prefix":"10.1111","volume":"28","author":[{"given":"Jing","family":"Tian","sequence":"first","affiliation":[{"name":"Central Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Li","sequence":"additional","affiliation":[{"name":"Central Hospital Affiliated to Shandong First Medical University  Jinan Shandong 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