Project Details

Impact of aspirin on endocannabinoid metabolism in pregnancy and preeclampsia

Jennifer Sequoia, MD, PhD

Summary

BACKGROUND: Preeclampsia (PE) affects 3-8% of pregnancies in the United States, accounting for the deaths of 70,000 women and 500,000 babies per year worldwide, and contributes to 20% of all preterm births. Aspirin (ASA) is the only preventative treatment available, yet not everyone responds to therapy and a better understanding of how it impacts individual lipid profiles in pregnancy can lead to more effective and targeted therapy. GAP: Studies to identify lipid profiles of ASA responders and non-responders have focused on classical targets of ASA therapy but fail to measure endocannabinoids, lipids that are dysregulated in PE and which are also metabolized by ASA-targeted enzymes. How ASA impacts endocannabinoid levels in pregnancy and PE is unknown. HYPOTHESIS: ASA-responsive endocannabinoids are dysregulated in PE. METHODS: To identify ASA-responsive lipids in pregnancy, endocannabinoids and related lipids will be measured in plasma from a prospective cohort of 20 pregnant people, before and after starting ASA therapy for PE prevention, and in 20 gestational age-matched controls who are not on ASA therapy (Aim 1). To identify endocannabinoids impacted by ASA in PE, plasma lipid levels will be measured in an established cohort of 41 people at the time of PE diagnosis and in 39 gestational age-matched controls, stratified by ASA therapy during pregnancy (Aim 2). RESULTS: Pending. IMPACT: By understanding the link between endocannabinoids, other lipids, and ASA therapy this research can help identify people who will most likely benefit from ASA therapy and uncover alternate lipid biosynthetic pathways to target for a personalized approach to PE prevention and therapy.