Role of epigenetics in pulmonary hypertension

Am J Physiol Cell Physiol. 2014 Jun 15;306(12):C1101-5. doi: 10.1152/ajpcell.00314.2013. Epub 2014 Apr 9.

Abstract

A significant amount of research has been conducted to examine the pathologic processes and epigenetic mechanisms contributing to peripheral hypertension. However, few studies have been carried out to understand the vascular remodeling behind pulmonary hypertension (PH), including peripheral artery muscularization, medial hypertrophy and neointima formation in proximal arteries, and plexiform lesion formation. Similarly, research examining some of the epigenetic principles that may contribute to this vascular remodeling, such as DNA methylation and histone modification, is minimal. The understanding of these principles may be the key to developing new and more effective treatments for PH. The purpose of this review is to summarize epigenetic research conducted in the field of hypertension that could possibly be used to understand the epigenetics of PH. Possible future therapies that could be pursued using information from these studies include selective histone deacetylase inhibitors and targeted DNA methyltransferases. Both of these could potentially be used to silence proproliferative or antiapoptotic genes that lead to decreased smooth muscle cell proliferation. Epigenetics may provide a glimmer of hope for the eventual improved treatment of this highly morbid and debilitating disease.

Keywords: DNA methylation; histone modification.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • DNA Methylation / genetics*
  • Epigenesis, Genetic / genetics*
  • Histone Deacetylase Inhibitors / therapeutic use
  • Histones / metabolism*
  • Humans
  • Hypertension, Pulmonary / drug therapy
  • Hypertension, Pulmonary / genetics*
  • Hypertension, Pulmonary / pathology
  • Reactive Oxygen Species / metabolism

Substances

  • Histone Deacetylase Inhibitors
  • Histones
  • Reactive Oxygen Species