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In this study, we evaluated whether the inhibition of class I HDACs can attenuate angiotensin II (ANG II)\u2013induced fibrogenesis and mitochondrial malfunction through its effects on reactive oxygen species (ROS) and calcium dysregulation in human cardiac fibroblasts (CFs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Seahorse XF24 extracellular flux analyser, fluorescence staining, Western blotting, HDAC activity assays and Transwell migration assay were used to study mitochondrial respiration, adenosine triphosphate (ATP) production, mitochondrial calcium uptake and ROS, HDAC expression and activity and fibroblast activity in CFs without (control) or with ANG II (100\u00a0nM) and\/or MS\u2010275 (HDAC class 1 inhibitor, 10\u00a0\u03bcM) for 24\u00a0h.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ANG II increased HDAC activity without changing protein expression in CFs. Compared with controls, ANG II\u2010treated CFs had greater migration activity, higher ATP production, maximal respiration and spare capacity with higher mitochondrial Ca<jats:sup>2+<\/jats:sup> uptake and ROS generation, which was attenuated by the administration of MS\u2010275. ANG II activated CFs by increasing mitochondrial calcium content and ATP production, which may be caused by increased HDAC activity. Inhibition of HDAC1 attenuated the effects of ANG II by reducing mitochondrial ROS generation and calcium overload.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Modulating mitochondrial function by regulation of HDAC may be a novel strategy for controlling CF activity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.13712","type":"journal-article","created":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T08:15:18Z","timestamp":1637050518000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Class I HDAC modulates angiotensin II\u2013induced fibroblast migration and mitochondrial overactivity"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8596-9977","authenticated-orcid":false,"given":"Tin Van","family":"Huynh","sequence":"first","affiliation":[{"name":"International Ph.D. Program in Medicine College of Medicine Taipei Medical University  Taipei 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