The underlying mechanism of preeclampsia by which an angiogenic imbalance results in systemic vascular endothelial dysfunction remains unclear. Complement activation directly induces endothelial dysfunction and is known to be involved in preeclampsia; nevertheless, the association between complement activation and angiogenic imbalance has not been established. This study aimed to evaluate whether angiogenic imbalance affects the expression and secretion of inhibitory complement factor H (CFH) in endothelial cells, resulting in complement activation and systemic vascular endothelial dysfunction. Viability of human umbilical vein endothelial cells (HUVECs) was assessed upon CFH knockdown by targeted-siRNA, and were incubated with complement factors. HUVECs were also treated with placental growth factor (PlGF) and/or soluble fms-like tyrosine kinase 1 (sFlt1), and CFH expression and secretion were measured. These cells were evaluated by cell viability assay and cell surface complement activation was quantified by immunocytochemical assessment of C5b-9 deposition. HUVECs transfected with CFH-siRNA had significantly lower viability than that of control cells. Moreover, the expression and secretion of CFH were significantly increased upon PlGF treatment compared with PlGF + sFlt1 combo. HUVECs treated with PlGF had less C5b-9 deposition and higher viability than HUVECs treated with PlGF + sFlt1. In summary, CFH was found to be essential for endothelial cell survival by inhibiting complement activation. An angiogenic imbalance, including decreased PlGF and increased sFlt1, suppresses CFH expression and secretion, resulting in complement activation on the surface of endothelial cells and systemic vascular endothelial dysfunction.

先兆子痫的潜在机制仍不清楚血管生成失衡导致全身血管内皮功能障碍。补体激活直接诱导内皮功能障碍，已知与先兆子痫有关；然而，补体激活和血管生成失衡之间的关联尚未确定。本研究旨在评估血管生成失衡是否影响内皮细胞中抑制性补体因子 H (CFH) 的表达和分泌，从而导致补体激活和全身血管内皮功能障碍。人脐静脉内皮细胞 (HUVEC) 的生存能力通过靶向 siRNA 对 CFH 敲低进行评估，并与补体因子一起孵育。HUVEC 还用胎盘生长因子 (PlGF) 和/或可溶性 fms 样酪氨酸激酶 1 (sFlt1) 处理，并测量了 CFH 表达和分泌。这些细胞通过细胞活力测定进行评估，细胞表面补体激活通过 C5b-9 沉积的免疫细胞化学评估进行量化。用 CFH-siRNA 转染的 HUVECs 的活力明显低于对照细胞。此外，与 PlGF + sFlt1 组合相比，PlGF 处理后 CFH 的表达和分泌显着增加。与用 PlGF + sFlt1 处理的 HUVEC 相比，用 PlGF 处理的 HUVEC 具有更少的 C5b-9 沉积和更高的活力。总之，发现 CFH 通过抑制补体激活对内皮细胞存活至关重要。血管生成失衡，包括 PlGF 减少和 sFlt1 增加，