Peixin Yang1, E Albert Reece. 1. Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
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. STUDY DESIGN: 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. CONCLUSION: 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.
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. STUDY DESIGN: 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. CONCLUSION: 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: Tarak H Patel; Hideo Kimura; Clifford R Weiss; Gregg L Semenza; Lawrence V Hofmann Journal: Cardiovasc Res Date: 2005-10-01 Impact factor: 10.787
Authors: Adolfo Correa; Suzanne M Gilboa; Lilah M Besser; Lorenzo D Botto; Cynthia A Moore; Charlotte A Hobbs; Mario A Cleves; Tiffany J Riehle-Colarusso; D Kim Waller; E Albert Reece Journal: Am J Obstet Gynecol Date: 2008-07-31 Impact factor: 8.661
Authors: Yanqing Wu; E Albert Reece; Jianxiang Zhong; Daoyin Dong; Wei-Bin Shen; Christopher R Harman; Peixin Yang Journal: Am J Obstet Gynecol Date: 2016-03-31 Impact factor: 8.661