Contribution of T lymphocytes in the development of maternal syndrome in Dahl SS rats

T 淋巴细胞在 Dahl SS 大鼠母体综合征发生中的作用

基本信息

  • 批准号:
    10076028
  • 负责人:
  • 金额:
    $ 6.37万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-02-01 至 2023-01-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Contribution of T lymphocytes in the development of maternal syndrome in Dahl SS rats Preeclampsia (PE) is a pregnancy-specific disorder that is characterized by hypertension and proteinuria (maternal syndrome) developing after the 20th week of gestation. PE is the leading cause of maternal morbidity and mortality in the United States, affecting about 5% of pregnancies. Furthermore, women with preexisting hypertension or chronic kidney disease have an increased risk for developing PE. With rates of PE rising in the United States, the exact mechanism(s) responsible for the pathogenesis of the disease remain undetermined. The current hypothesis is thought to be a two-step process: 1) improper placentation and remodeling of the spiral arteries and 2) development of maternal syndrome. Current animal models require either a surgical or pharmacologic intervention to develop PE-like phenotypes; however, these models are not capable of investigating the first step in the disease process. An animal model that spontaneously develops PE is preferential to investigate the full course in the development of PE. Preliminary data demonstrate that the Dahl salt-sensitive (SS) rat is just such an animal model to help investigate mechanisms of PE since it spontaneously develops PE while remaining on a low salt (0.4% NaCl) diet. The present studies will test the general hypothesis that maternal syndrome in Dahl SS rats is an outcome of improper placentation resulting in an increased infiltration of T lymphocytes into kidney and placental tissues causing subsequent release of proinflammatory cytokines that contributes to the development hypertension and renal damage. To test this hypothesis, two specific aims are proposed. AIM 1 will first characterize the maternal syndrome phenotype in the Dahl SS rat on a low salt diet. To understand how T lymphocytes contribute to the pathogenesis, AIM 2 will explore the role of proinflammatory cytokine production due to infiltration of T lymphocytes into renal and placental tissue of Dahl SS rats. We have observed pregnancy- specific increases in blood pressure and proteinuria that are associated with increased infiltration of T lymphocytes into renal and placental tissues. This phenotype is consistent with what is observed in clinical settings, and this model provides a unique opportunity to study the whole disease process of PE. Completion of the studies in this proposal will establish a clear role for T lymphocytes in the pathogenesis of PE, and potentially uncover therapeutic targets to effectively treat PE.
项目摘要 T淋巴细胞在Dahl SS大鼠母源性综合征发病中的作用 (PE)是一种妊娠特异性疾病,其特征是高血压和蛋白尿(母体综合征) 在怀孕20周后发育。PE是孕产妇发病率和死亡率的主要原因, 在美国,约有5%的孕妇受到影响。此外,患有高血压或慢性 肾脏疾病增加了发生PE风险。随着美国PE率的上升, 导致该疾病发病机制的机制仍不确定。目前的假设是 被认为是一个两步过程:1)胎盘形成不当和螺旋动脉重塑,2) 产妇综合征的发展。目前的动物模型需要手术或药理学 干预开发PE样表型;然而,这些模型不能研究第一步 在疾病过程中。自发发展PE的动物模型优先用于研究完整的 在体育发展的过程中。初步数据表明,达尔盐敏感(SS)大鼠正是这样的 动物模型,以帮助研究PE的机制,因为它自发地发展PE,同时保持 低盐(0.4%NaCl)饮食。目前的研究将测试一般假设,母亲综合征, Dahl SS大鼠是胎盘形成不当导致T淋巴细胞浸润增加的结果。 肾脏和胎盘组织引起促炎细胞因子的随后释放, 发展为高血压和肾损害。为了检验这一假设,提出了两个具体目标。要求1 将首先在低盐饮食的Dahl SS大鼠中表征母体综合征表型。了解如何 T淋巴细胞参与发病机制,AIM 2将探讨促炎细胞因子产生的作用 由于T淋巴细胞浸润到DahlSS大鼠的肾脏和胎盘组织中。我们观察到怀孕- 与T细胞浸润增加相关的血压和蛋白尿的特异性增加 淋巴细胞进入肾脏和胎盘组织。这种表型与临床上观察到的一致。 该模型为研究PE的整个疾病过程提供了一个独特的机会。完成 这项研究将明确T淋巴细胞在PE发病机制中的作用, 发现有效治疗PE的治疗靶点。

项目成果

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John H Dasinger其他文献

John H Dasinger的其他文献

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{{ truncateString('John H Dasinger', 18)}}的其他基金

Nox2-derived oxidative stress produced by T cells contributes to the development of maternal syndrome in the Dahl salt-sensitive rat.
T 细胞产生的 Nox2 衍生氧化应激导致达尔盐敏感大鼠发生母体综合征。
  • 批准号:
    10370733
  • 财政年份:
    2022
  • 资助金额:
    $ 6.37万
  • 项目类别:
Nox2-derived oxidative stress produced by T cells contributes to the development of maternal syndrome in the Dahl salt-sensitive rat.
T 细胞产生的 Nox2 衍生氧化应激导致达尔盐敏感大鼠发生母体综合征。
  • 批准号:
    10563126
  • 财政年份:
    2022
  • 资助金额:
    $ 6.37万
  • 项目类别:

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