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
- 批准号:10437699
- 负责人:
- 金额:$ 50.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-07-05 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:Abnormal placentationAddressAfrican AmericanAge of OnsetAngiogenesis InhibitorsApoptosisBiologicalBiological MarkersBlood CirculationBody mass indexCalibrationCardiovascular DiseasesCharacteristicsClinicalClinical ManagementDataDetectionDevelopmentDiagnosisDiscipline of obstetricsDiscriminationEndoglinEtiologyExperimental ModelsFetusFunctional disorderGestational AgeGoalsGrowthHELLP SyndromeHMGB1 ProteinHealthHospitalizationHumanIatrogenesisImmuneIn VitroIncidenceInflammationInjuryKnowledgeLeadLifeLinear RegressionsLiteratureMaternal AgeMaternal MortalityMeasuresMetadataMissionModelingModificationMolecularMonitorMorbidity - disease rateMothersMusNatureNested Case-Control StudyOrganOutcomePGF genePathogenesisPathway interactionsPatternPhenotypePlacentaPlasmaPre-EclampsiaPregnancyPremature BirthPreventionProbabilityProspective cohortProteinuriaPublic HealthReportingResearchResearch DesignRiskRoleSamplingStimulusStressSymptomsSyncytiotrophoblastSyndromeTestingToll-like receptorsUnited States National Institutes of HealthWeightWomancase controlclinical diagnosiscohortdensitydisabilityearly onsetendothelial dysfunctionepidemiology studyextracellular vesiclesfetalhazardimprovedindexinginfant morbidity/mortalityinnovationinsightmaternal morbiditymaternal outcomematernal riskmicrovesiclesmortalitynovelnovel markerpathophysiology of preeclampsiaplacental protein 13potential biomarkerpregnancy hypertensionpressurepreventprospectiveresponsescreeningsecondary outcomesexsystemic inflammatory responsetargeted treatment
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)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(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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