title: The role of redox signaling in epigenetics and cardiovascular disease.
abstract: CONCLUSIONS
  The term epigenetics refers to the changes in the phenotype and gene expression that occur without alterations in the DNA sequence. There is a rapidly growing body of evidence that epigenetic modifications are involved in the pathological mechanisms of many cardiovascular diseases (CVDs), which intersect with many of the pathways involved in oxidative stress.
  
  
  BACKGROUND
  Most studies relating epigenetics and human pathologies have focused on cancer. There has been a limited study of epigenetic mechanisms in CVDs. Although CVDs have multiple established genetic and environmental risk factors, these explain only a portion of the total CVD risk. The epigenetic perspective is beginning to shed new light on how the environment influences gene expression and disease susceptibility in CVDs. Known epigenetic changes contributing to CVD include hypomethylation in proliferating vascular smooth muscle cells in atherosclerosis, changes in estrogen receptor-α (ER-α) and ER-β methylation in vascular disease, decreased superoxide dismutase 2 expression in pulmonary hypertension (PH), as well as trimethylation of histones H3K4 and H3K9 in congestive heart failure.
  
  
  RESULTS
  In this review, we discuss the epigenetic modifications in CVDs, including atherosclerosis, congestive heart failure, hypertension, and PH, with a focus on altered redox signaling.
  
  
  CONCLUSIONS
  As advances in both the methodology and technology accelerate the study of epigenetic modifications, the critical role they play in CVD is beginning to emerge. A fundamental question in the field of epigenetics is to understand the biochemical mechanisms underlying reactive oxygen species-dependent regulation of epigenetic modification.
authors.affiliation: Department of Medicine, Section of Cardiology, University of Chicago, Chicago, Illinois 60637, USA. gkim1@medicine.bsd.uchicago.edu
authors.forename: Gene H
authors.initials: GH
authors.lastname: Kim
authors.forename: John J
authors.initials: JJ
authors.lastname: Ryan
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Archer
mesh_terms: D002318:Cardiovascular Diseases / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation; D004777:Environment; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction; D012307:Risk Factors; D015398:Signal Transduction
chemical_list: D006657:Histones