Endothelial cells exposed to preeclamptic placental macrophages show increased oxidative stress and impaired angiogenesis in vitro.

Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by endothelial dysfunction and immune dysregulation, with delivery remaining the only curative treatment. Although aberrant macrophage (MΦ) polarization has been implicated in PE, the mechanisms by which placental MΦs contribute to endothelial dysfunction remain incompletely understood. We hypothesized that MΦs isolated from preeclamptic placentas secrete factors that promote endothelial activation, oxidative stress, and impaired angiogenesis compared with MΦ from normal pregnancies (NP). Primary placental MΦs from NP and PE women were co-cultured with human umbilical vein endothelial cells (HUVECs) in a transwell culture system, and endothelial oxidative stress, angiogenic capacity, viability, and activation marker expression were assessed alongside circulating cytokines and growth factors. Women with PE exhibited significantly elevated blood pressure, increased body mass index, reduced gestational age at delivery, and lower fetal weight compared with NP controls (p < 0.01). NP serum demonstrated significantly higher MCP-1 (300 ± 233 vs. 124 ± 89.9 pg/mL; p = 0.0348) and IL-4 concentrations (45.4 ± 41.9 vs. 7.84 ± 10.7 pg/mL; p = 0.0106), with a trend toward higher epidermal growth factor levels. PE serum demonstrated significantly higher PDGF-BB (2.46 × 104 ± 1.55 × 104 vs 1.19 × 104 ± 7.43 × 103 pg/mL; p = 0.0080). HUVECs co-cultured with PE-derived MΦ exhibited increased mitochondrial superoxide production (18.22 ± 6.81 vs. 9.40 ± 5.73%; p < 0.001), reduced tube formation and mesh area (p < 0.05), and increased preproendothelin-1 and ICAM-1 (p < 0.05). Collectively, these findings demonstrate that soluble factors released by placental MΦs from preeclamptic pregnancies promote endothelial oxidative stress, activation, and impaired angiogenesis in vitro, supporting a role for MΦ-endothelial crosstalk in PE-associated vascular dysfunction.