Perinatal & Pediatric
Mid-Pregnancy Extracellular Vesicle Proteomic Signatures Differentiate Preeclampsia and Normotensive Pregnancies Brandie DePaoli Taylor* Brandie DePaoli Taylor DePaoli Taylor DePaoli Taylor DePaoli Taylor DePaoli Taylor DePaoli Taylor DePaoli Taylor DePaoli Taylor University of Texas Medical Branch
Background: Preeclampsia (PE) causes maternal morbidity and mortality, but early detection is limited by its molecular heterogeneity. Extracellular vesicles (EVs) modify key biological processes, and their protein cargo may provide biological insight into PE pathogenesis. However, studies have not extensively examined EVs and their cargo before PE diagnosis.
Methods: We obtained stored plasma (18-20 weeks gestation) from 163 PE cases and 325 normotensive controls in the SCOPE cohort. EVs were isolated by size exclusion chromatography and characterized by size/quantity. Logistic regression estimated associations between EV concentration and PE, adjusting for maternal demographic and behavioral factors. Secondary analyses examined preterm PE, severe PE, and PE with small for gestational age. Proteomic profiling of randomly selected EV samples (50 PE and 50 controls) was performed by DIA mass spectrometry followed by protein-protein interaction and Ingenuity Pathway Analysis (IPA). Differential expression was determined using a log2 fold-change cutoff of ±1.5 with false discovery rate correction.
Results: Higher EV concentrations were associated with preterm PE (OR 1.54, 95%CI 1.10–2.19) and severe PE (OR 1.38, 95%CI 1.05–1.84) (figure 1). Proteomic analyses identified 31 upregulated and 14 downregulated EV proteins in PE compared to controls. IPA revealed dysregulated coagulation and extracellular matrix remodeling pathways consistent with inflammation-induced endothelial injury and hypercoagulability. Downregulated apolipoproteins suggested impaired lipid transport, impacting placental development. Network and canonical pathway analyses further demonstrated dysregulated canonical and non-canonical Wnt signaling, which may drive abnormal placentation.
Conclusions: EVs are elevated in preterm and severe PE as early as 18 weeks gestation. These EVs have unique proteomic signatures but further studies are needed to validate EV-associated dysregulation of Wnt signaling.
