Class I HDAC modulates angiotensin II–induced fibroblast migration and mitochondrial overactivity

Tin Van Huynh, Lekha Rethi, Cheng Chih Chung, Yung Hsin Yeh, Yu Hsun Kao, Yi Jen Chen

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Background: Inhibition of histone deacetylases (HDACs) attenuates cardiac fibrosis. In this study, we evaluated whether the inhibition of class I HDACs can attenuate angiotensin II (ANG II)–induced fibrogenesis and mitochondrial malfunction through its effects on reactive oxygen species (ROS) and calcium dysregulation in human cardiac fibroblasts (CFs). Methods: 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 nM) and/or MS-275 (HDAC class 1 inhibitor, 10 μM) for 24 h. Results: ANG II increased HDAC activity without changing protein expression in CFs. Compared with controls, ANG II-treated CFs had greater migration activity, higher ATP production, maximal respiration and spare capacity with higher mitochondrial Ca2+ uptake and ROS generation, which was attenuated by the administration of MS-275. 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. Conclusions: Modulating mitochondrial function by regulation of HDAC may be a novel strategy for controlling CF activity.

Original languageEnglish
Article numbere13712
JournalEuropean Journal of Clinical Investigation
Issue number4
Publication statusPublished - Apr 2022


  • angiotensin II
  • cardiac fibrosis
  • class I histone deacetylases
  • mitochondria
  • reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry


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