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HDAC6 is associated with the formation of aortic dissection in human

Xian Guo1, Ze-Min Fang1, Xiang Wei1,2,3,4

  • 1Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Molecular Medicine (Cambridge, Mass.)
|March 31, 2019
PubMed

Insights

Histone deacetylase HDAC6 is reduced in aortic dissection (AD), impacting extracellular matrix genes and providing a potential therapeutic target for AD treatment by modulating histone post-translational modifications.

Area of Science:

  • Cardiovascular Biology
  • Epigenetics
  • Molecular Pathology

Background:

  • Aortic dissection (AD) involves vascular smooth muscle cell loss, altered elastic fibers, and inflammation.
  • The specific post-translational modification (PTM) mechanisms underlying AD pathogenesis remain largely unknown.

Purpose of the Study:

  • To investigate the role of histone deacetylase HDAC6 in the molecular mechanisms of type A aortic dissection (TAAD).
  • To identify specific histone PTMs regulated by HDAC6 in TAAD and their downstream targets.

Main Methods:

  • Analyzed aortic tissue samples from TAAD patients and coronary artery disease (CAD) controls.
  • Utilized chromatin immunoprecipitation (ChIP)-PCR to identify genes regulated by H3K23ac.
  • Employed tubastatin A, an HDAC6 inhibitor, to explore downstream effects in vitro and in vivo.

Main Results:

  • Reduced HDAC6 protein levels were observed in TAAD aortas compared to controls.
  • Specific histone acetylation patterns (increased H3K23ac, H4K12ac; decreased H3K18ac, H4K8ac, H4K5ac) were associated with TAAD.
  • H3K23ac enrichment was found in extracellular matrix-related genes in TAAD samples, and HDAC6 was shown to regulate H4K20me2 and p-MEK1/2.

Conclusions:

  • HDAC6 plays a critical role in TAAD development through the regulation of H3K23ac, H4K20me2, and p-MEK1/2.
  • Targeting HDAC6 and related histone PTMs offers a potential therapeutic strategy for TAAD.
Abstract

Keywords:
Aortic dissectionH3K23acH4K20me2HDAC6Histone post-translational modificationSignaling pathway

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