PAVA-Study: Preeclampsia Associated Vascular Aging – long-term follow up and prevention strategies

Study Objective: The clinical observation that women after preeclampsia are at high risk for early onset cardiovascular disease, featuring increased diseases associated mortality, has led to the hypothesis that the endothelial status of these women is characterized by an early onset of aging. We aim to elucidate the nature of the link between endothelial aging and pregnancy disorders like preeclampsia, dominated by endothelial dysfunction. Do endothelial changes precede pregnancy and cause preeclampsia and later early onset aging, or does preeclampsia first initiates premature endothelial aging in the affected individuals? The goal of this proposal is to assess the cardiovascular health of women 10 – 20 years post preeclampsia in comparison to those with uneventful pregnancies. Furthermore, the potential endothelial protective effect of the NO donor pentaerytrithyltetranitrate (PETN) will be examined. The long-term aim of this proposal is to facilitate a prospective longitudinal study on the effect of PETN on vascular aging in women after preeclampsia in order to asses, if treatment of endothelial dysfunction during pregnancy could diminish endothelial aging and thus, premature cardiovascular morbidity and mortality in millions of women. Method: The running in vivo study will asses the cardiovascular health status of women 10 – 20 years after pregnancy. Patients with a history of preeclampsia will be compared to matched controls, as well as with patients who had received PETN treatment or palcebo. Analysis includes physical evaluation, total vascular resistance, carotid intima media thickness, blood pressure, flow mediated dilation, critical flicker frequency, puls-wave velocity, augmentation index, basic lab analysis, as well as multiplex screening. In addition, the study will be elaborated in vitro through the analysis of a possible induction of premature senescence by manipulation of HUVEC cells with preeclampsia simulating stress via sFlt-1, Endoglin-1 or serum of preeclampsia patients, and the change in cellular behavior with addition of PETN to selected stress inducers.