The role of ANGPT2 in pathogenesis of preeclampsia

Preeclampsia, a placenta disorder characterized by angiogenic imbalance, remains etiologically undefined. This research investigated the role of angiopoietin-2 (ANGPT2) dysregulation in preeclampsia-associated placental angiogenesis defects.

Placenta tissues from three preeclampsia patients and three matched controls underwent data-independent acquisition (DIA) proteomic profiling. ANGPT2, prioritized via KEGG and DO analyses, was validated using RT-PCR, Western blot and immunohistochemistry in preeclampsia placentae. JEG3 cells were transfected with ANGPT2 shRNA to generate conditioned medium (CM) for HUVECs migration, invasion and tubule formation assays. The levels of ANGPT2, ANGPT1 and VEGF in CM were analyzed using ELISA. Placenta angiogenesis was evaluated using CD34 immunostaining.

Proteomics analysis revealed 437 differentially expressed proteins, and identified ANGPT2 as the most significantly dysregulated protein in preeclampsia placenta. The expression of ANGPT2 was increased in preeclampsia placenta detected by RT-PCR, Western blot and immunohistochemistry, while VEGF gene expression was decreased. Knockdown of ANGPT2 via ANGPT2 shRNA in JEG3 cells downregulated ANGPT2 expression and upregulated gene expression of VEGF and ANGPT1. The concentration of ANGPT2 was reduced and the concentration of ANGPT1 and VEGF was increased in CM from ANGPT2 shRNA transfected JEG3 cells, migration and invasion abilities of HUVECs were suppressed with a reduction in number of migration and invasion cells. Meanwhile, tubule formation was also inhibited with a reduction in branching points and meshes. The number of CD34⁺ vessels per visual field was reduced in preeclampsia placenta.

The results indicated that imbalance between ANGPT2 and VEGF in preeclampsia placenta impaired angiogenesis, contributing to preeclampsia pathogenesis.