This study is focused on the molecular events that lead to the cellular movements and proliferative changes in vessel walls following injury. The early growth response factor-1 (Egr-1) gene is linked to the host response to vascular and inflammatory stress.1 When endothelium is exposed to injury, it releases fibroblast growth factor-2 (FGF-2) from cell walls and this binds to the fibroblast growth factor receptor-1 (FGFR-1) and induces the expression of the Egr-1 transcription factor.2 Egr-1 is not present in unperturbed endothelium but is immediately and rapidly induced by injury. It has been likened to a master switch. Thus, it is dramatically present in endothelium and vascular smooth muscle cells and tissue phagocytes after injury. It is important in regulation of genes mediating inflammatory and procoagulant processes. It is also important in angiogenesis. It has been linked to both the initiation and the progression of atherosclerotic vascular lesions.3–5
In recent work, we have described endothelial cell activation6 and proinflammatory cytokine production7 in the umbilical vascular tree of the placenta villi in thrombotic placental vasculopathy. We studied pregnant women identified to have vascular disease in the placenta by a high-resistance umbilical artery Doppler flow velocity waveform pattern.8 We demonstrated that endothelial cells isolated from the placental villi were activated and producing proinflammatory cytokines. We also showed a factor in fetal plasma from these pregnancies, capable of inducing this change in endothelial cells in culture.9,10
In this study, we sought to explore further the origin of the vascular pathology identified by the high-resistance umbilical artery Doppler flow velocity waveform. We hypothesised that injury to the endothelium in placental vascular disease would be evidenced by upregulation of the Egr-1 transcription factor. We therefore measured Egr-1 gene expression in placental villous endothelium. We also studied the release of FGF-2 by vascular trees and measured FGF-2 in fetal plasma and upregulation of the receptor FGFR-1 by measuring gene expression of the FGFR-1 by the endothelium.