Identifying Inflammatory and Endothelial Mechanisms promoting Cardiac Deformation in Women with a History of Preeclampsia

PROJECT SUMMARY Women with a history of preeclampsia (preE) are at a 2-fold higher risk of cardiovascular disease and develop subclinical cardiovascular disease 5 years earlier than women with normotensive pregnancies; however, the mechanism remains unknown. In our K23 study of 150 participants including 90 with history of preeclampsia and 60 with normotensive pregnancy 2-10 years postpartum, we found evidence of subclinical cardiovascular disease (myocardial deformation and vascular dysfunction) in those with history of PreE. Our central hypothesis is that women with a history of preeclampsia will demonstrate long-term elevations in biomarkers of inflammation and endothelial dysfunction and that these will be directly associated with the observed subclinical cardiovascular disease. Utilizing the K23 biorepository of 150 samples, we will measure levels of inflammatory cytokines, endothelial biomarkers and endothelial microvesicles. We will then examine the relationship of these biomarkers to measurements of myocardial deformation (CMRI) and vascular functional (EndoPAT and SphygmoCor). Upon completion of these aims, we expect to establish endothelial dysfunction and chronic inflammation as the mechanisms responsible for the myocardial deformation and vascular dysfunction in women with history of preeclampsia 2-10 years postpartum. These insights will significantly advance our understanding of these mechanisms and guide future pharmacological interventions.