Epigenetic reprogramming in atherosclerosis

Curr Atheroscler Rep. 2015;17(2):476. doi: 10.1007/s11883-014-0476-3.

Abstract

Recent data support the involvement of epigenetic alterations in the pathogenesis of atherosclerosis. The most widely investigated epigenetic mechanism is DNA methylation although also histone code changes occur during the diverse steps of atherosclerosis, such as endothelial cell proliferation, vascular smooth muscle cell (SMC) differentiation, and inflammatory pathway activation. In this review, we focus on the main genes that are epigenetically modified during the atherogenic process, particularly nitric oxide synthase (NOS), estrogen receptors (ERs), collagen type XV alpha 1 (COL15A1), vascular endothelial growth factor receptor (VEGFR), and ten-eleven translocation (TET), which are involved in endothelial dysfunction; gamma interferon (IFN-γ), forkhead box p3 (FOXP3), and tumor necrosis factor-α (TNF-α), associated with atherosclerotic inflammatory process; and p66shc, lectin-like oxLDL receptor (LOX1), and apolipoprotein E (APOE) genes, which are regulated by high cholesterol and homocysteine (Hcy) levels. Furthermore, we also discuss the role of non-coding RNAs (ncRNA) in atherosclerosis. NcRNAs are involved in epigenetic regulation of endothelial function, SMC proliferation, cholesterol synthesis, lipid metabolism, and inflammatory response.

Publication types

  • Review

MeSH terms

  • Atherosclerosis / genetics*
  • Cholesterol / metabolism
  • DNA Methylation
  • Epigenesis, Genetic*
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylases / metabolism
  • Humans
  • Lipid Metabolism
  • RNA, Small Untranslated

Substances

  • Histone Deacetylase Inhibitors
  • RNA, Small Untranslated
  • Cholesterol
  • Histone Deacetylases