title: Role of HIF-1α in maternal hyperglycemia-induced embryonic vasculopathy.
abstract: OBJECTIVE
  Maternal diabetes adversely impacts embryonic vasculogenesis, which results in embryonic vasculopathy. The purpose of our study is to determine whether hypoxia inducible factor (HIF)-1α plays a role in diabetic embryonic vasculopathy.
  
  
  METHODS
  Levels of HIF-1α were determined in mouse conceptuses. Conceptuses on day 7 of pregnancy were cultured under euglycemic (150 mg/dL glucose) and hyperglycemic (300 mg/dL) conditions with or without AdCA5, or in the presence or absence of 2.0 μg/mL human recombinant thioredoxin, an endogenous antioxidant protein. AdCA5 is an adenovirus encoding a constitutively active form of HIF-1α.
  
  
  RESULTS
  Maternal diabetes significantly reduced HIF-1α protein expression. The administration of 1 μL (1 × 10(7) infectious units/mL) per 1 mL culture medium AdCA5 completely reversed hyperglycemia-reduced vasculature morphological scores and vascular endothelial growth factor expression. Thioredoxin treatment reversed hyperglycemia-reduced HIF-1α levels.
  
  
  CONCLUSIONS
  We conclude that reduced HIF-1α plays a critical role in the induction of diabetic embryonic vasculopathy, and that oxidative stress is implicated in hyperglycemia-induced HIF-1α reduction.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Peixin
authors.initials: P
authors.lastname: Yang
authors.forename: E Albert
authors.initials: EA
authors.lastname: Reece
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003470:Culture Media; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005260:Female; D006943:Hyperglycemia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D013879:Thioredoxins / Q000494:pharmacology; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism; D015017:Yolk Sac / Q000098:blood supply*
chemical_list: D000975:Antioxidants; D003470:Culture Media; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D042442:Vascular Endothelial Growth Factors; D013879:Thioredoxins