Single-Cell transcriptomic profiling of the vascular endothelium in hypertensive disorders of pregnancy

Hypertensive disorders of pregnancy, particularly preeclampsia, are major drivers of maternal mortality, yet their systemic impact on the maternal endothelium remains poorly understood at cellular resolution. This study applied single-cell RNA sequencing to peripheral blood-derived endothelial colony-forming cells (ECFCs) to map endothelial heterogeneity in Uzbek pregnant women with preeclampsia (PE, n=22), gestational hypertension (GH, n=20), and normotensive controls (CTRL, n=23). We analyzed 48,512 high-quality single ECFC transcriptomes, identifying 8 distinct endothelial subclusters. A pro-inflammatory subcluster (EC-3) was significantly expanded in PE (18.2% of cells) compared to GH (9.5%) and CTRL (4.1%, p<0.001), while an angiogenic subcluster (EC-6) was depleted. Cells within the inflammatory EC-3 cluster from PE patients showed marked upregulation of adhesion molecules (SELE, VCAM1), chemokines (CXCL8, CCL2), and EDN1. A rare, severe-PE-specific subpopulation (EC-3b) expressing interferon-response genes was identified. The inflammatory transcriptomic signature strongly correlated with clinical severity (SBP: ρ=0.78, p<0.001). A model combining EC-3 abundance and inflammatory score discriminated PE from CTRL with high accuracy (AUC=0.97).