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Increased m6A methylation level is associated with the progression of human abdominal aortic aneurysm

Yuchen He1, Jia Xing2, Shiyue Wang1

  • 1Department of Vascular Surgery, The First Hospital of China Medical University, Key Laboratory of Pathogenesis, Prevention, and Therapeutics of Aortic Aneurysm, Shenyang 110001, China.

Annals of Translational Medicine
|February 12, 2020
PubMed
Abstract

Insights

N6-methyladenosine (m6A) levels are elevated in abdominal aortic aneurysm (AAA) and linked to rupture risk. Key m6A modulators like YTHDF3 and FTO play significant roles in AAA pathogenesis.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cardiovascular Research

Background:

  • Abdominal aortic aneurysm (AAA) pathogenesis is complex and not fully understood.
  • The role of N6-methyladenosine (m6A) RNA modification in AAA remains largely unexplored.
  • This study investigates m6A RNA methylation and its modulators in human AAA tissues.

Purpose of the Study:

  • To investigate m6A RNA methylation levels in AAA tissues compared to healthy aortas.
  • To identify and analyze the expression of key m6A RNA modulators in AAA.
  • To explore the correlation between m6A modification, its modulators, and AAA characteristics, including rupture risk.

Main Methods:

  • Comparative analysis of AAA tissues (n=32) and healthy aortas (n=12).
  • Quantification of mRNA m6A status.
  • Quantitative PCR (qPCR) and Western blot for m6A modulator expression.
  • Immunohistochemistry (IHC) for cellular localization of modulators.

Main Results:

  • Significantly increased m6A levels were observed in AAA tissues compared to healthy aortas.
  • Elevated m6A levels correlated with an increased risk of AAA rupture.
  • Key m6A modulators (YTHDF1, YTHDF3, FTO, METTL14) showed aberrant expression correlated with m6A levels.
  • YTHDF3 expression was associated with increased rupture risk; METTL14 with inflammatory infiltrates; FTO with smooth muscle cells; YTHDF3 with macrophage infiltrate.

Conclusions:

  • This is the first study to report m6A modification in human AAA tissues.
  • m6A modulators, including YTHDF3, FTO, and METTL14, are implicated in AAA pathogenesis.
  • Findings suggest a potential role for epigenetic alterations in clinical AAA development and progression.
Keywords:
Abdominal aortic aneurysm (AAA)N6-methyladenosine RNA methyltransferase (m6A RNA methyltransferase)N6-methyladenosine modification (m6A modification)epigenetics

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