Preeclampsia-associated changes in umbilical cord stromal VEGFR-2 and EV-mediated in vitro angiogenesis
Placenta, cilt.186, ss.99-109, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 186
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.placenta.2026.09.023
- Dergi Adı: Placenta
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CINAHL, EMBASE, MEDLINE
- Sayfa Sayıları: ss.99-109
- Anahtar Kelimeler: Angiogenesis, Extracellular vesicle, Preeclampsia, Umbilical cord, VEGFR-2, Wharton's jelly
- Ankara Üniversitesi Adresli: Evet
Özet
Introduction: Preeclampsia (PE) is associated with abnormal placental development, vascular dysfunction, and increased maternal–fetal morbidity. VEGFR-2 is a key mediator of angiogenesis; however, its expression in umbilical cord (UC) stromal compartments, particularly in early-onset (EOPE) and late-onset PE (LOPE), remains insufficiently characterized. We investigated VEGFR-2 expression in distinct UC stromal regions and assessed the angiogenic capacity of human UC-derived multipotent stromal cells (hUC-MSCs) and their extracellular vesicles (EVs). Methods: UC samples from 66 pregnant women were classified as control, EOPE, or LOPE. Cases with intrauterine growth restriction and maternal comorbidities were excluded to minimize potential confounding. Morphometric analysis, immunofluorescence, qRT-PCR, and in vitro HUVEC tube formation assays were performed. Results: PE cases showed significantly increased umbilical artery lumen area and artery lumen index compared with healthy term controls, with no significant differences between EOPE and LOPE. VEGFR-2 expression showed marked regional heterogeneity, with lower levels in the subepithelial stroma than in intervascular and perivascular regions. Although stromal VEGFR-2 protein levels did not differ significantly between PE and control tissues, median signals in the intervascular and perivascular regions were approximately 15–38% lower in PE groups, accompanied by reduced VEGFR-2 mRNA expression. PE-derived hUC-MSCs also exhibited decreased VEGFR-2 expression and reduced angiogenic capacity, while their EVs showed impaired in vitro HUVEC tube formation activity. Conclusion: PE is associated with altered UC vascular morphology and impaired VEGFR-2-related angiogenic activity in hUC-MSCs and their EVs. These alterations appear largely independent of whether PE develops early or late in pregnancy.