Mechanisms of Cardiorenal Disease following Preeclampsia

子痫前期是当今全球孕产妇发病率和死亡率的主要原因之一， 影响到美国大约5%的怀孕。先兆子痫的特征是 由于妊娠后半期高血压和蛋白尿的进行性发展， 以及全身性内皮功能障碍。对母亲的风险不会随着分娩而结束 然而，胎儿胎盘单位。经历过先兆子痫的女性患子痫的风险更高。 高血压、中风、心脏病和肾脏疾病，但导致 先兆子痫后的心血管和肾脏疾病尚不清楚。因此，有一个至关重要的 有必要确定子痫前期后妇女的最佳治疗方案。 不幸的是，缺乏一种自发的先兆子痫动物模型一直是 机制和潜在治疗靶点的确定中和随诊 先兆子痫。我们令人兴奋的初步数据表明，达尔盐敏感(达尔S)大鼠 妊娠期自发性地发展为先兆子痫的特征 人类疾病，加速了心肾疾病和持续存在的免疫激活 产后。这个模型将允许我们通过研究 子痫前期妊娠对血管内皮功能及肾脏进展的长期影响 既往有高血压的女性的疾病和免疫激活，并确定 强化围产期血压管理将改善长期心血管健康 结果。该项目将检验先兆子痫会导致持续的 产后免疫激活使母亲容易发生内皮细胞病变 功能障碍和慢性肾脏病。这项研究将对该领域产生重大影响，1)提供 了解导致心肾功能长期风险增加的机制 子痫前期妊娠后的疾病和2)提供临床前研究为决策提供参考 关于对有患先兆子痫风险的妇女的围产期护理。因此，这项工作 具有重要的临床和翻译价值，因为这些发现最终可以帮助我们 新的治疗目标，以改善有子痫前期和子痫病史的妇女的预后 确定治疗方案以降低这些患者心血管死亡的长期风险 女人。

Preeclampsia is one of the leading causes of maternal morbidity and death worldwide today, affecting approximately 5% of all pregnancies in the United States. Preeclampsia is characterized by hypertension during the second half of pregnancy and progressive development of proteinuria, along with systemic endothelial dysfunction. The risk to the mother does not end with delivery of the fetoplacental unit however. Women who experience preeclampsia have a heightened risk for hypertension, stroke, heart disease, and kidney disease, but the mechanisms that contribute to cardiovascular and renal disease following preeclampsia are unclear. Therefore, there is a vital need for the determination of optimal therapeutic regimens for women following preeclampsia. Unfortunately, the lack of a spontaneous animal model of preeclampsia has been an obstacle in the identification of the mechanisms and potential therapeutic targets during and following preeclampsia. Our exciting preliminary data show that the Dahl Salt Sensitive (Dahl S) rat spontaneously develops characteristics of preeclampsia during pregnancy that are similar to the human disease and has accelerated cardiorenal disease and immune activation that persists postpartum. This model will allow us to significantly advance our knowledge by examining the long-term impact of preeclamptic pregnancy on endothelial function, progression of kidney disease, and immune activation in females with pre-existing hypertension and determine if intensive perinatal management of blood pressure will improve long term cardiovascular health outcomes. This project will test the central hypothesis that preeclampsia results in a lasting postpartum immunological activation that predisposes the mother to progression of endothelial dysfunction and CKD. This research will have a significant impact on the field by 1) providing an understanding of mechanisms that contribute to the long term increased risk of cardiorenal disease following preeclamptic pregnancy and 2) providing preclinical studies to inform decisions regarding the perinatal care for women at risk of developing preeclampsia. Therefore, this work has important clinical and translational value as these findings could ultimately help us identify novel therapeutic targets to improve outcomes for women with a history of preeclampsia and identify treatment regimens to attenuate the long term risk of cardiovascular death in these women.