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HDAC9 in the Injury of Vascular Endothelial Cell Mediated by P38 MAPK Pathway

Xi Kuang1,2, Shuang Chen1,2, Jitong Lao1,2

  • 1Department of Neurology, The First Affiliated Hospital of Hainan Medical University, Haikou, China.

Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
|December 22, 2021
PubMed

Insights

Histone deacetylase 9 (HDAC9) promotes inflammatory injury in vascular endothelial cells, contributing to atherosclerosis and ischemic stroke. Inhibiting HDAC9 with sodium valproate may offer a potential treatment strategy.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Neuroscience

Background:

  • Atherosclerosis (AS) and ischemic stroke significantly impact human health.
  • Genome-wide association studies link histone deacetylase 9 (HDAC9) expression in atheromatous plaques to ischemic stroke.
  • The precise molecular mechanisms remain unclear.

Purpose of the Study:

  • To investigate the role of HDAC9 in oxidized low-density lipoprotein (ox-LDL)-induced inflammatory injury in vascular endothelial cells.
  • To explore the involvement of the P38 mitogen-activated protein kinase (P38 MAPK) pathway in HDAC9-mediated AS.
  • To evaluate the therapeutic potential of HDAC9 inhibition for ischemic stroke.

Main Methods:

  • Knockdown of HDAC9 in vascular endothelial cells using short hairpin RNA (shRNA).
  • Assessment of P38 MAPK phosphorylation levels.
  • Treatment with sodium valproate (SVA), a HDAC9 inhibitor, and SB203580, a P38 MAPK inhibitor.

Main Results:

  • HDAC9 knockdown reduced ox-LDL-induced inflammatory injury in vascular endothelial cells.
  • HDAC9 regulates the phosphorylation of P38 MAPK, a key inflammatory pathway.
  • Sodium valproate (SVA) and SB203580 antagonized inflammatory damage in vascular endothelial cells.

Conclusions:

  • HDAC9 mediates ox-LDL-induced inflammatory injury in vascular endothelial cells by modulating P38 MAPK phosphorylation, contributing to AS.
  • HDAC9 is a potential therapeutic target for preventing and treating atherosclerotic plaques.
  • Sodium valproate (SVA) shows promise as a potential drug for ischemic stroke prevention and treatment.

Keywords:
HDAC 9P38 MAPKatherosclerosisischemic strokesodium valproatevascular endothelial cells

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