2. Academic Validation
  3. Promotional effects of HIF1α and KDM3A interaction on vascular smooth muscle cells in thoracic aortic dissection

Promotional effects of HIF1α and KDM3A interaction on vascular smooth muscle cells in thoracic aortic dissection

  • Epigenomics. 2022 Mar;14(5):227-241. doi: 10.2217/epi-2021-0147.
Zheyong Liang 1,  Qi Liang 2,  Wei Zhang 3,  Lei Zheng 4,  Xuji Shen 4,  Yongjian Zhang 1 5
Affiliations

Affiliations

  • 1 Department of Cardiovascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.
  • 2 Department of Cardiology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.
  • 3 Department of Cardiovascular Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5Road, Xi'an, 710004, Shaanxi, China.
  • 4 School of Pharmaceutical Sciences, Xi'an Medical University, Xi'an, 710021, Shaanxi, China.
  • 5 Cardiovascular Research Centre, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China.
PMID: 35172598 DOI: 10.2217/epi-2021-0147
Abstract

Aim: The current study was performed to define the role of KDM3A in thoracic aortic dissection (TAD). Methods: The binding of HIF1α and KDM3A in HES1 was detected by ChIP and dual-luciferase reporter gene assay. Loss and gain-of function assays of HIF1α, KDM3A and HES1 were further performed in Ang-II-induced mouse aortic smooth muscle cell line (MOVAS) cells. Lastly, in vivo TAD models were established. Results: HIF1α was highly expressed in TAD. KDM3A promoted the transcription activation of HES1. HIF1α enhanced the proliferation and migration of Ang-II-induced MOVAS cells, in addition to increasing thoracic aorta dilation to induce TAD formation in vivo. Silencing of HES1 reversed the effects of HIF1α in vivo and in vitro. Conclusion: The findings indicated that interaction between HIF1α and KDM3A enhances the proliferation and migration of MOVAS cells to induce TAD.

Keywords

HES1; HIF1α; KDM3A; demethylation; migration; proliferation; thoracic aortic dissection; vascular smooth muscle cells.

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