Complement activation by an angiogenic imbalance leads to systemic vascular endothelial dysfunction: A new proposal for the pathophysiology of preeclampsia

概要

〔目 的(Purpose))
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 preeclampsiai 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.

〔方法ならびに成績(Methods/Resuits)〕
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 (P1GF) and/or soluble fms-like tyrosine kinase 1(sFltl),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 P1GF treatment compared with P1GF + sFltl combo. HUVECs treated with P1GF had less C5b-9 deposition and higher viability than HUVECs treated with P1GF + sFltl.

〔総 括(Conclusion)]
CFH was found to be essential for endothelial cell survival by inhibiting complement activation. An angiogenic imbalance, including decreased P1GF and increased sFltl, suppresses CFH expression and secretion, resulting in complement activation on the surface of endothelial cells and systemic vascular endothelial dysfunction.