Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
Am J Obstet Gynecol. 2011 Apr;204(4):332.e1-7. doi: 10.1016/j.ajog.2011.01.012. Epub 2011 Feb 23.
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.
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.
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.
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.
母体糖尿病对胚胎血管发生有不利影响，导致胚胎血管病变。我们的研究目的是确定缺氧诱导因子 (HIF)-1α 是否在糖尿病胚胎血管病变中发挥作用。
测定了小鼠胚胎中的 HIF-1α 水平。在正常血糖（150mg/dL 葡萄糖）和高血糖（300mg/dL）条件下，以及在存在或不存在 AdCA5 或 2.0μg/mL 人重组硫氧还蛋白（一种内源性抗氧化蛋白）的情况下，对妊娠第 7 天的胚胎进行培养。AdCA5 是一种编码 HIF-1α 组成性激活形式的腺病毒。
母体糖尿病显著降低了 HIF-1α 蛋白表达。给予 1μL（1×10(7)感染单位/mL）/1mL 培养基 AdCA5 可完全逆转高血糖降低的血管形态评分和血管内皮生长因子表达。硫氧还蛋白处理可逆转高血糖降低的 HIF-1α 水平。
我们得出结论，HIF-1α 的减少在诱导糖尿病胚胎血管病变中起关键作用，氧化应激与高血糖诱导的 HIF-1α 减少有关。
