title: Angiogenic Gene Expression in Down Syndrome Fetal Hearts.
abstract: BACKGROUND
  Forty percent of Down syndrome (DS) fetuses have congenital heart defects (CHD). An abnormal angiogenic environment has been described in euploid fetuses with CHD. However, the underlying pathophysiologic pathway that contributes to CHD in DS remains unknown. The objective was to compare the expression of angiogenic factors and chronic hypoxia genes in heart tissue from DS and euploid fetuses with and without CHD.
  
  
  METHODS
  The gene expression profile was determined by real-time PCR quantification in heart tissue from 33 fetuses with DS, 23 euploid fetuses with CHD and 23 control fetuses.
  
  
  RESULTS
  Angiogenic factors mRNA expression was significantly increased in the DS group compared to the controls (soluble fms-like tyrosine kinase-1, 81%, p = 0.007; vascular endothelial growth factor A, 57%, p = 0.006, and placental growth factor, 32%, p = 0.0227). Significant increases in the transcript level of hypoxia-inducible factor-2α and heme oxygenase 1 were also observed in the DS group compared to the controls. The expression of angiogenic factors was similar in DS fetuses and CHD euploid fetuses with CHD.
  
  
  CONCLUSIONS
  Abnormal angiogenesis was detected in the hearts of DS fetuses with and without CHD. Our results suggest that DS determines an intrinsically angiogenic impairment that may be present in the fetal heart.
authors.affiliation: Maternal and Child Health and Development Network II (SAMID II) RD12/0026, Institute of Health Carlos III, Madrid, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Sánchez
authors.forename: Carmen
authors.initials: C
authors.lastname: Domínguez
authors.forename: Aina
authors.initials: A
authors.lastname: Ruiz
authors.forename: Irene
authors.initials: I
authors.lastname: Ribera
authors.forename: Jaume
authors.initials: J
authors.lastname: Alijotas
authors.forename: Lluís
authors.initials: L
authors.lastname: Cabero
authors.forename: Elena
authors.initials: E
authors.lastname: Carreras
authors.forename: Elisa
authors.initials: E
authors.lastname: Llurba
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D004314:Down Syndrome / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006330:Heart Defects, Congenital / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000191:economics*; D000072483:Placenta Growth Factor / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000072105:Superoxide Dismutase-1 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D042501:Angiogenic Proteins; D051792:Basic Helix-Loop-Helix Proteins; D051547:Heme Oxygenase-1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000072483:Placenta Growth Factor; D012333:RNA, Messenger; D000072105:Superoxide Dismutase-1; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human; C000608036:PGF protein, human; C467484:VEGFA protein, human; C496541:HMOX1 protein, human; C501162:FLT1 protein, human