title: Epigenetics of hypoxic pulmonary arterial hypertension following intrauterine growth retardation rat: epigenetics in PAH following IUGR.
abstract: BACKGROUND
  Accumulating evidence reveals that intrauterine growth retardation (IUGR) can cause varying degrees of pulmonary arterial hypertension (PAH) later in life. Moreover, epigenetics plays an important role in the fetal origin of adult disease. The goal of this study was to investigate the role of epigenetics in the development of PAH following IUGR.
  
  
  METHODS
  The IUGR rats were established by maternal undernutrition during pregnancy. Pulmonary vascular endothelial cells (PVEC) were isolated from the rat lungs by magnetic-activated cell sorting (MACS). We investigated epigenetic regulation of the endothelin-1 (ET-1) gene in PVEC of 1-day and 6-week IUGR rats, and response of IUGR rats to hypoxia.
  
  
  RESULTS
  The maternal nutrient restriction increased the histone acetylation and hypoxia inducible factor-1α (HIF-1α) binding levels in the ET-1 gene promoter of PVEC in IUGR newborn rats, and continued up to 6 weeks after birth. These epigenetic changes could result in an IUGR rat being highly sensitive to hypoxia later in life, causing more significant PAH or pulmonary vascular remodeling.
  
  
  CONCLUSIONS
  These findings suggest that epigenetics is closely associated with the development of hypoxic PAH following IUGR, further providing a new insight for improved prevention and treatment of IUGR-related PAH.
authors: Department of Neonatology, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, P,R, China.
authors: Xue-Feng
authors: XF
authors: Xu
authors: Ying
authors: Y
authors: Lv
authors: Wei-Zhong
authors: WZ
authors: Gu
authors: Li-Li
authors: LL
authors: Tang
authors: Jia-Kai
authors: JK
authors: Wei
authors: Li-Yan
authors: LY
authors: Zhang
authors: Li-Zhong
authors: LZ
authors: Du
mesh_terms: D000107:Acetylation; D000199:Actins / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites; D001794:Blood Pressure / Q000235:genetics*; D002469:Cell Separation / Q000379:methods; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics*; D005434:Flow Cytometry; D006657:Histones / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008168:Lung / Q000098:blood supply*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D011651:Pulmonary Artery / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000199:Actins; D019332:Endothelin-1; D006657:Histones; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C497444:Hif1a protein, rat; C498862:Acta2 protein, rat