ANGIOTENSINOGEN VARIANTS AND ADVERSE PREGNANCY OUTCOMES

描述：（改编自研究者摘要）正常妊娠早期， 母体血管阻力降低，伴随着20%的 100%增加母体血容量。与此同时，子宫动脉 经历了深刻的重塑和扩张-称为"生理变化"- 为发育中的孕体提供充足的血流。故障卷 扩张和失败或异常的生理变化与 各种常见的妊娠并发症，包括先兆子痫，宫内 生长迟缓（IUGR）和早产。的分子变体 血管紧张素原基因，增加血管紧张素原的表达，在某些 当地系统，使妇女容易患上先兆子痫和相关妊娠 并发症这一竞争性的更新提出了一个假设， 疾病相关血管紧张素原等位基因促进螺旋动脉异常 重塑并抑制母体血浆体积膨胀。三个相互关联 提出了以下方法：1）受影响的姐妹对连锁分析， 血管紧张素原和其他相关基因的多态性，2）基因表达 螺旋动脉重建的定量组织学研究， 现有的大量人类妊娠组织，以及3）转基因小鼠 和人类研究来评估新描述的旁分泌肾小管肾素 血管紧张素原系统在母体血容量扩张中的作用的 研究人员指出，这项工作可能会导致预测和诊断测试， 表明妇女在怀孕早期患并发症的风险增加， 允许改进的监测、早期诊断和新的机会， 治疗他们进一步指出，这项研究的最终目标是 制定更好的预防措施和有效的治疗方法， 常见的妊娠障碍通过对特定基因的理解， 他们指出，他们可能会发现，一旦有希望， 治疗，如低剂量阿司匹林，在一些患者中确实有作用。最后， 他们指出，可能会发现新的生物途径， 治疗策略

DESCRIPTION: (Adapted from Investigator's Abstract) Early in normal gestation, there is a decrease in maternal vascular resistance accompanied by a 20% of 100% expansion of maternal blood volume. At the same time, the uterine arteries undergo profound remodeling and dilation -- termed "physiologic change" -- to provide adequate blood flow to the developing conceptus. Failed volume expansion and failed or abnormal physiologic change are associated with a variety of common pregnancy complications, including preeclampsia, intrauterine growth retardation (IUGR), and preterm labor. Molecular variants of the angiotensinogen gene, which increase angiotensinogen expression in certain local systems, predispose women to develop preeclampsia and related pregnancy complications. This competing renewal proposes to test the hypothesis that disease-associated angiotensinogen alleles promote abnormal spiral artery remodeling and inhibit maternal plasma volume expansion. Three interrelated approaches are proposed: 1) an affected sister-pair linkage analysis of polymorphisms in angiotensinogen and other relevant genes, 2) gene expression and quantitative histology studies of spiral artery remodeling using an existing large collection of human pregnancy tissues, and 3) transgenic mouse and human studies to evaluate the newly-described paracrine tubular renin angiotensinogen system's role in maternal blood volume expansion. The investigators state that this work may lead to predictive and diagnostic tests that indicate a woman's increased risk for complications early in pregnancy, allowing improved monitoring, earlier diagnosis, and new opportunities for treatment. They further state that the ultimate goal of this research is the development of improved preventive measures and effective treatments for these common pregnancy disorders. Through an understanding of particular genetic subsets of preeclampsia, they note that they may find that once promising therapies, such as low-dose aspirin, do have a role in some patients. Finally, they note that new biologic pathways may be discovered that suggest novel therapeutic strategies.