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Long non-coding RNA CDKN2B-AS1 reduces inflammatory response and promotes cholesterol efflux in atherosclerosis by

Haocheng Li1, Song Han1, Qingfeng Sun1

  • 1Department of Vascular Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, P. R. China.

Aging
|March 31, 2019
PubMed
Abstract

Insights

Long non-coding RNA CDKN2B-AS1 inhibits atherosclerosis by downregulating ADAM10. This mechanism reduces inflammation and enhances cholesterol efflux, offering a potential therapeutic target for atherosclerosis.

Area of Science:

  • Molecular Biology
  • Cardiovascular Research
  • RNA Biology

Background:

  • Long non-coding RNAs (lncRNAs) are implicated in atherosclerosis development via inflammatory pathways.
  • The specific role of lncRNA CDKN2B-AS1 in atherosclerosis, particularly its interaction with ADAM10, requires further investigation.

Purpose of the Study:

  • To investigate the role of lncRNA CDKN2B-AS1 in atherosclerosis.
  • To elucidate the mechanism by which CDKN2B-AS1 influences ADAM10 expression and function.
  • To assess the impact of CDKN2B-AS1 and ADAM10 on macrophage cholesterol efflux and inflammatory responses.

Main Methods:

  • Quantified CDKN2B-AS1 and ADAM10 expression in atherosclerotic tissues and THP-1 macrophage foam cells.
  • Assessed macrophage cholesterol efflux rates.
  • Analyzed the interaction between CDKN2B-AS1 and ADAM10.
  • Manipulated CDKN2B-AS1 and ADAM10 expression to evaluate effects on inflammation and cholesterol efflux.
  • Validated findings in an atherosclerosis mouse model.

Main Results:

  • Atherosclerotic plaques and foam cells showed decreased CDKN2B-AS1 and increased ADAM10 expression.
  • Overexpressing CDKN2B-AS1 or silencing ADAM10 reduced lipid accumulation and increased cholesterol efflux.
  • Nuclear CDKN2B-AS1 binds to DNMT1, enhancing methylation of the ADAM10 promoter.
  • This epigenetic regulation suppressed atherosclerotic inflammation and promoted cholesterol efflux.

Conclusions:

  • lncRNA CDKN2B-AS1 inhibits ADAM10 transcription through DNMT1-mediated DNA methylation.
  • This mechanism effectively mitigates the inflammatory response in atherosclerosis.
  • CDKN2B-AS1 promotes cholesterol efflux, suggesting its potential as a therapeutic target.
Keywords:
ADAM10DNMT1atherosclerosischolesterol effluxinflammatory responselong non-coding RNA CDKN2B-AS1

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