Epigenetics: A Potential Mechanism Involved in the Pathogenesis of Various Adverse Consequences of Obstructive Sleep Apnea

Int J Mol Sci. 2019 Jun 15;20(12):2937. doi: 10.3390/ijms20122937.

Abstract

Epigenetics is defined as the heritable phenotypic changes which do not involve alterations in the DNA sequence, including histone modifications, non-coding RNAs, and DNA methylation. Recently, much attention has been paid to the role of hypoxia-mediated epigenetic regulation in cancer, pulmonary hypertension, adaptation to high altitude, and cardiorenal disease. In contrast to sustained hypoxia, chronic intermittent hypoxia with re-oxygenation (IHR) plays a major role in the pathogenesis of various adverse consequences of obstructive sleep apnea (OSA), resembling ischemia re-perfusion injury. Nevertheless, the role of epigenetics in the pathogenesis of OSA is currently underexplored. This review proposes that epigenetic processes are involved in the development of various adverse consequences of OSA by influencing adaptive potential and phenotypic variability under conditions of chronic IHR. Improved understanding of the interaction between genetic and environmental factors through epigenetic regulations holds great value to give deeper insight into the mechanisms underlying IHR-related low-grade inflammation, oxidative stress, and sympathetic hyperactivity, and clarify their implications for biomedical research.

Keywords: DNA methylation; epigenetics; histone modification; intermittent hypoxia with re-oxygenation; non-coding RNA; obstructive sleep apnea.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA Methylation
  • Endothelins / metabolism
  • Epigenesis, Genetic*
  • Gene Expression Regulation
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Histones / metabolism
  • Humans
  • Hypoxia / genetics
  • Hypoxia / metabolism
  • Hypoxia-Inducible Factor 1 / metabolism
  • MicroRNAs / genetics
  • NF-kappa B / metabolism
  • RNA, Untranslated / genetics
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Sleep Apnea, Obstructive / etiology*
  • Sleep Apnea, Obstructive / metabolism
  • Toll-Like Receptors / metabolism

Substances

  • Endothelins
  • Histones
  • Hypoxia-Inducible Factor 1
  • MicroRNAs
  • NF-kappa B
  • RNA, Untranslated
  • Reactive Oxygen Species
  • Toll-Like Receptors