Angiotensin 2 Receptor (AT2R) Expression/Activation in Endothelial Cells in Preeclampsia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 166
- 试验地点
- 1
- 主要终点
- To test if ex-vivo treatment of AT2R agonists reverses the endothelial dysfunction and improves vasoconstriction in the preeclamptic vessels.
研究概览
简要总结
The investigators will collect omental tissue (research surgical excision) and placental tissue (standard of care clinical delivery) from both preeclamptic and non-preeclamptic women during their c-section and use these samples to study the blood vessels, specifically the expression/activation of the AT2R.
详细描述
Trial Design: The study is a comparison of two cohorts, those with and without preeclampsia during pregnancy. The team plans to investigate role of FABP4, PFAS and AT2 in modulation of vascular function/dysfunction using vessels isolated from the omental biopsies. The investigators will examine evidence of fetal vascular dysfunction mediated by decreased expression of AT2 in preeclampsia using vessels isolated from the placentas.
Study Population: The study will include pregnant women. The pregnant women will participate in the omental tissue collection, placenta collection, and the medical record review.
The study is expects a maximum enrollment of 166 pregnant women. This is because 52 omental biopsies and 104 placentas are required to meet proposed statistical considerations. Participants have the option of providing just one or both of the specimens. There is a possibility as few as 52 participants could be enrolled and a maximum of 166 participants could be enrolled to meet this requirement. There is an additional 10 participants enrollment built into the enrollment number to allow for replacement of subjects based on lack of clinical data in some participants, failure of tissue viability and hence experiments, and thus a maximum of 166 (156+10) participants could be enrolled.
This required enrollment is divided into two cohorts based on the diagnosis of preeclampsia: specimens in which the woman was diagnosed with preeclampsia during her pregnancy, and 26 of each type of specimen in which the woman was not diagnosed with preeclampsia during her pregnancy. Additionally, each cohort will be divided into two groups based on gender of the fetus.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Ages 18 to 40 years old
- •Singleton gestation between 28 weeks, 0 days and 41 weeks, 0 days gestational age at the time of consent
- •Undergoing caesarean section, either planned or otherwise with or without trial of labor
排除标准
- •Treatment of severe hypertension by antihypertensive or use of magnesium sulfate after the patient is hospitalized for the diagnosis of preeclampsia.
- •Any major fetal structural anomalies or aneuploidies
- •Undergoing cesarean section for placental abruption or bleeding complications.
- •Singleton gestation not within 36 weeks, 0 days and 41 weeks, 0 days gestational age at the time of enrollment (delivery)
结局指标
主要结局
To test if ex-vivo treatment of AT2R agonists reverses the endothelial dysfunction and improves vasoconstriction in the preeclamptic vessels.
时间窗: 1 year
The researchers will quantify vascular AT2R expression and vascular function in placental and omental arteries of preeclamptic vs normal pregnant women. Vascular function studies will also test if ex vivo treatment with AT2R agonist reverses endothelial dysfunction and vasoconstriction in preeclamptic vessels.
To test AT2R mediated mechanisms on endothelial derived hyperpolarizing factor, nitric oxide and prostacyclin pathway of vascular relaxation to examine AT2's role in vaso-relaxation and AT2R mediated vasoconstrictor pathway will be defined.
时间窗: 1 year
To test the AT2R-mediated mechanisms, endothelium-derived hyperpolarizing factor (EDHF), nitric oxide, and prostacyclin (PGI2) pathways of vascular relaxation and AT1R-mediated vasoconstrictor pathways will be determined. Also, the expression of endothelial nitric oxide synthase, its activity state, and signaling components of EDHF and PGI2 pathways, as well as nitrate/nitrite and PGI2 production and changes in membrane potential, will be measured
Quantify the vascular AT2R expression and vascular function in placental and omental vascular arteries in both preeclamptic and controlled pregnancies.
时间窗: 1 year
The researchers will measure the amount and distribution of vascular angiotensin II type 1 receptor (AT1R) and AT2R during normal human pregnancy and in preeclampsia. The researchers will assess if AT2R expression varies with severity of preeclampsia. Based on pilot data, the researchers expect decreased AT2R and increased AT1R protein levels in preeclamptic vs normotensive vessels.
次要结局
未报告次要终点