Immune activating syncytiotrophoblast microvesicles and danger associated molecular patterns in preeclampsia risk

先兆子痫风险中免疫激活合体滋养层微泡和危险相关分子模式

基本信息

项目摘要

PROJECT SUMMARY/ABSTRACT Despite decades of research, preeclampsia remains a serious public health burden. The only treatment for preeclampsia is delivery, which often leads to iatrogenic preterm birth. Unfortunately, clinical symptoms do not indicate progression to severe maternal outcomes. Thus, preeclampsia remains a significant contributor to both maternal and infant morbidity and mortality. Health risks extend beyond pregnancy, as women with preeclampsia are more likely to develop cardiovascular disease later in life. There is a significant need to improve understanding of preeclampsia etiology and to define the heterogeneous nature of the syndrome. As systemic inflammation and endothelial dysfunction are hallmarks of preeclampsia, novel immune stimulating syncytiotrophoblast microvesicles (STBEVs) are implicated as potential biomarkers to monitor placental health. Small studies report elevated plasma STBEVs in preeclampsia after diagnosis and STBEVs trigger inflammation and endothelial dysfunction in experimental models. However, large scale epidemiologic investigations of STBEVs and their influence on immune activating components, such as danger associated molecular patterns (DAMPs), have not been conducted in preeclampsia prior to clinical diagnosis. Our long-term goal is to identify biomarkers that can distinguish pathophysiological preeclampsia phenotypes. The current proposal will address gaps in the literature to advance our understanding of STBEVs in preeclampsia. The central hypothesis is that circulating STBEVs lead to higher levels of circulating DAMPs and antiangiogenic molecules that trigger the clinical symptoms of preeclampsia. The current proposal will utilize a nested case-control study design and obtain plasma and prospectively collected metadata from 280 women who developed preeclampsia and 560 controls (selected by incidence density sampling) in the Screening for Obstetric and Pregnancy Endpoints cohort. The specific aims are to; 1) Determine if STBEVs are elevated in women with preeclampsia prior to clinical diagnosis. 2) Determine if maternal/fetal factors influence STBEV levels. 3) Determine the relationship between STBEV's and circulating levels of DAMPs and antiangiogenic molecules previously implicated in preeclampsia. 4) Determine if STBEVs can improve preeclampsia phenotype discrimination. This study design is an efficient approach to measure STBEVs prior to preeclampsia diagnosis. Innovative features of this study include measuring STBEVs with increased sensitivity and less sample volume than the standard developed by Knight et al in 1998, delineating the role of STBEV's in preeclampsia and utilizing latent mixture modelling to identify preeclampsia phenotypes. Our proposal is significant, as clinical symptoms do not identify women who will progress to severe outcomes and truly require induced delivery (current treatment). Thus, progression towards redefining PE may reduce unnecessary hospitalization, early delivery, and missed opportunities to prevent maternal and fetal morbidity and mortality.
项目总结/文摘

项目成果

期刊论文数量(0)
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Brandie DePaoli Taylor其他文献

Preconception emChlamydia trachomatis/em seropositivity and fecundability, live birth, and adverse pregnancy outcomes
衣原体感染前血清阳性与受孕能力、活产和不良妊娠结局
  • DOI:
    10.1016/j.fertnstert.2024.12.017
  • 发表时间:
    2025-06-01
  • 期刊:
  • 影响因子:
    7.000
  • 作者:
    Yajnaseni Chakraborti;Stefanie N. Hinkle;Jørgen Skov Jensen;Catherine L. Haggerty;Toni Darville;Sunni L. Mumford;Enrique F. Schisterman;Robert M. Silver;Brandie DePaoli Taylor
  • 通讯作者:
    Brandie DePaoli Taylor

Brandie DePaoli Taylor的其他文献

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{{ truncateString('Brandie DePaoli Taylor', 18)}}的其他基金

Evaluating the intersection between sexually transmitted infections, inflammation and reproductive success
评估性传播感染、炎症和生殖成功之间的交叉点
  • 批准号:
    10338181
  • 财政年份:
    2020
  • 资助金额:
    $ 50.73万
  • 项目类别:
Evaluating the intersection between sexually transmitted infections, inflammation and reproductive success
评估性传播感染、炎症和生殖成功之间的交叉点
  • 批准号:
    10442247
  • 财政年份:
    2020
  • 资助金额:
    $ 50.73万
  • 项目类别:
Evaluating the intersection between sexually transmitted infections, inflammation and reproductive success
评估性传播感染、炎症和生殖成功之间的交叉点
  • 批准号:
    10576339
  • 财政年份:
    2020
  • 资助金额:
    $ 50.73万
  • 项目类别:
Evaluating the intersection between sexually transmitted infections, inflammation and reproductive success
评估性传播感染、炎症和生殖成功之间的交叉点
  • 批准号:
    9887442
  • 财政年份:
    2020
  • 资助金额:
    $ 50.73万
  • 项目类别:
Evaluating the intersection between sexually transmitted infections, inflammation and reproductive success
评估性传播感染、炎症和生殖成功之间的交叉点
  • 批准号:
    10115581
  • 财政年份:
    2020
  • 资助金额:
    $ 50.73万
  • 项目类别:
Immune activating syncytiotrophoblast microvesicles and danger associated molecular patterns in preeclampsia risk
先兆子痫风险中免疫激活合体滋养层微泡和危险相关分子模式
  • 批准号:
    10655445
  • 财政年份:
    2019
  • 资助金额:
    $ 50.73万
  • 项目类别:
Immune activating syncytiotrophoblast microvesicles and danger associated molecular patterns in preeclampsia risk
先兆子痫风险中免疫激活合体滋养层微泡和危险相关分子模式
  • 批准号:
    10441912
  • 财政年份:
    2019
  • 资助金额:
    $ 50.73万
  • 项目类别:

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