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.

Public Health Relevance

Preeclampsia affects ~5-10% of all pregnancies and increases the risk of cardiovascular and kidney disease in the 10-15 years after pregnancy. This proposal will use a novel spontaneous animal model of preeclampsia to explore the mechanisms responsible for the development and progression of postpartum cardiorenal disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL134711-03
Application #
9612569
Study Section
Hypertension and Microcirculation Study Section (HM)
Program Officer
Mcdonald, Cheryl
Project Start
2017-01-01
Project End
2021-12-31
Budget Start
2019-01-01
Budget End
2019-12-31
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Mississippi Medical Center
Department
Pharmacology
Type
Schools of Medicine
DUNS #
928824473
City
Jackson
State
MS
Country
United States
Zip Code
39216