课题基金 / 基金详情

Alcohol and Maternal Uterine Vascular Adaptations in Pregnancy

Alcohol and Maternal Uterine Vascular Adaptations in Pregnancy
妊娠期酒精与母体子宫血管适应
批准号:
9053392
负责人:
Jayanth Ramadoss
金额:
$32.74万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2015
资助国家:
美国
项目状态:
已结题
起止时间:
2015-04-15 至 2020-03-31

项目摘要

项目成果

Jayanth Ramadoss的其他基金

相似基金

相关文献

中文摘要
翻译
孕妇孕期酒精滥用可导致胎儿酒精谱系障碍(FASD),这是一种以一系列生长和发育缺陷为特征的终身残疾。目前估计FASD在美国学龄儿童中的患病率约为2-5%。努力成功地预防或改善乙醇的致畸作用
英文摘要
DESCRIPTION (provided by applicant): Alcohol & Maternal Uterine Vascular Adaptations in Pregnancy Maternal alcohol abuse during pregnancy can result in Fetal Alcohol Spectrum Disorders (FASD), a lifelong disability characterized by a range of growth and developmental deficits. Current estimates of FASD prevalence is about 2-5% among young school children in the United States. Efforts to successfully prevent or ameliorate the teratogenic effects of ethanol have been impeded, at least in part, by a limited understanding of alcohol's complex mechanisms of action involving multiple organ systems. A normal pregnancy is associated with major uterine circulatory adaptations that directly relates to fetal growth, neonatal birth weights and survival. A cardinal feature of fetal alcohol syndrome is growth restriction, but traditionally alcohol studies have focused on brain/behavioral deficits, and little attention has been paid to critical gestational uterine vascular adaptations. We herein show novel preliminary data that alcohol impairs the exquisite regulation of gestational uterine circulatory adaptations in rat bing alcohol model. We herein hypothesize that chronic binge alcohol exposure during pregnancy impairs maternal uterine artery vascular adaptations via endothelial nitric oxide (NO) system dysregulation. Aim#1 will test the hypothesis that binge alcohol exposure in pregnancy leads to impaired endothelium-dependent maternal uterine artery relaxation. Following binge paradigm, we will assess growth indices, and utilize wire myography to study agonist-induced uterine artery relaxation in endothelium-intact/denuded vessels from saline control, pair-fed nutrition control, and alcohol rats. Aim#2 will test if binge alcohol impairs uterine artery relaxation via endothelium-derived NO relative to prostacyclin/endothelium-derived hyperpolarizing factor, decreases uterine artery NO production, endothelial NO synthase (eNOS) expression, and impairs eNOS multi-site phosphorylation. Aim#3 will test if binge alcohol decreases uterine artery NO, decreases excitatory Pser1177eNOS levels, and increases inhibitory Pthr495eNOS levels via ERK/AMPK pathway, and alcohol effects on endothelial [Ca+2]i transients. In Aims#2 and #3, we will assess uterine artery relaxation after blocking major vasodilatory pathways and conduct mechanistic studies with/without eNOS activity/multi-site phosphorylation-regulating pathway antagonists via RT-PCR, immunoblotting, histology, fluorescent imaging and spectrophotometry. Simultaneous [Ca2+]i-NO fluorescent imaging will be performed utilizing high-speed excitation/emission wavelength switching system. Our proposal explores a new frontier of gestational alcohol research by developing the first mechanistic framework for binge alcohol-induced uterine artery adaptations and identifying alcohol targets in an in vivo model. In alignment with NIAAA FY14 Strategic Plan, our proposal utilizes powerful methods and presents a new maternal-inclusive paradigm to the FAS field and predicts that a more effective intervention will require innovative pharmacologic targeting of maternal systems, especially the critical uterine circulation, in order to predict and propose a therapy that will have a real promie as a preventive strategy.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
ELECTRONIC CIGARETTE VAPING & VASCULAR SEQUELAE IN THE UTERUS DURING PREGNANCY.
  • 批准号:
    10540752
  • 项目类别:
  • 资助金额:
    $38.84万
  • 财政年份:
    2021
  • 负责人:
    Jayanth Ramadoss
  • 依托单位:
ELECTRONIC CIGARETTE VAPING & VASCULAR SEQUELAE IN THE UTERUS DURING PREGNANCY.
  • 批准号:
    10459954
  • 项目类别:
  • 资助金额:
    $22.3万
  • 财政年份:
    2021
  • 负责人:
    Jayanth Ramadoss
  • 依托单位:
ELECTRONIC CIGARETTE VAPING & VASCULAR SEQUELAE IN THE UTERUS DURING PREGNANCY.
  • 批准号:
    10324577
  • 项目类别:
  • 资助金额:
    $40.23万
  • 财政年份:
    2021
  • 负责人:
    Jayanth Ramadoss
  • 依托单位:
ELECTRONIC CIGARETTE VAPING & VASCULAR SEQUELAE IN THE UTERUS DURING PREGNANCY
  • 批准号:
    10116886
  • 项目类别:
  • 资助金额:
    $12.12万
  • 财政年份:
    2021
  • 负责人:
    Jayanth Ramadoss
  • 依托单位:
国内基金
海外基金
Agonist-GPR119-Gs复合物的结构生物学研究
  • 批准号:
    32000851
  • 项目类别:
    青年科学基金项目
  • 资助金额:
    24.0万元
  • 批准年份:
    2020
  • 负责人:
    乔安娜
  • 依托单位: