HETEROGENEITY OF ENDOTHELIAL CELLS REGARDING VON WILLEBRAND FACTOR TRANSCRIPTIONAL RESPONSE TO HYPOXIA

摘要

BACKGROUND: Von Willebrand factor (VWF) is an endothelial specific pro-coagulant protein with a major role in thrombosis. We have demonstrated that hypoxia induces VWF upregula-tion in endothelial cells in vitro and in vivo. Specifically we demonstrated that VWF upregulation in vivo occurs in lung, heart, liver and brain but not kidney. We explored the mechanism of VWF promoter activation and demonstrated that lung-specific enhancer (I51HSS) of the VWF gene that is located in intron 51, and the YY1 transacting factor that interact with this region, participate in hypoxia-induced upregulation of VWF in lung endothelial cells (ECs). We have now evidence that endothelial cells of distinct organs exhibit heterogeneity in their response to hypoxia with regard to VWF expression, and this has functional thrombotic consequences.