Role of HIF-1[alpha] in maternal hyperglycemia-induced embryonic vasculopathy.
Yang, Peixin PhD; Reece, Albert E. MD, PhD, MBA
[Miscellaneous Article] American Journal of Obstetrics & Gynecology. 204(4):332e1-332e7, April 2011.

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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)-1[alpha] plays a role in diabetic embryonic vasculopathy.

STUDY DESIGN: Levels of HIF-1[alpha] 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 [mu]g/mL human recombinant thioredoxin, an endogenous antioxidant protein. AdCA5 is an adenovirus encoding a constitutively active form of HIF-1[alpha].

RESULTS: Maternal diabetes significantly reduced HIF-1[alpha] protein expression. The administration of 1 [mu]L (1 x 107 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-1[alpha] levels.

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

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