Aspirin to prevent cardiac dysfunction in preeclampsia

ABSTRACT Preeclampsia (PE) is a disease of late pregnancy characterized by hypertension and organ damage, which not only increases peripartum morbidity but is associated with the postpartum development of heart failure, including myocardial fibrosis and systolic heart failure. Despite two decades of research demonstrating this association and a large public health burden, the molecular mechanisms mediating PE-induced postpartum heart failure remain poorly understood and therapies to prevent this outcome are lacking. One potential trigger may be the profibrotic growth factor Activin A, a member of the transforming growth factor beta family produced by the placenta and inflammatory cells. Using a randomized mechanistic clinical trial of aspirin vs. placebo for patients with preeclampsia, integrated with studies of the mechanisms by which aspirin and Activin A might affect the heart, we will dramatically advance knowledge of cardiac dysfunction in preeclampsia and its possible treatments. We pursue two specific aims to answer these questions. AIM 1 is a randomized trial to test whether aspirin improves cardiac function and decreases Activin A in women with preeclampsia. AIM 2 Identifies how increased plasma Activin A during pregnancy causes postpartum cardiac dysfunction and how aspirin prevents it. This project innovates methodologically and at the bench in order to dramatically advance our understanding of a major cause of morbidity and mortality in women globally.