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)-1a plays a role in diabetic embryonic vasculopathy.

STUDY DESIGN: Levels of HIF-1a 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-1a.

RESULTS: Maternal diabetes significantly reduced HIF-1a 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-1a levels.

CONCLUSION: We conclude that reduced HIF-1a plays a critical role in the induction of diabetic embryonic vasculopathy, and that oxidative stress is implicated in hyperglycemia-induced HIF-1a reduction.

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