Von Willebrand factor (VWF) is expressed exclusively in endothelial cells (EC) and megakaryocyte.VWF gene expression is regulated by a complex system that includes distinct regulatory regions that target expression to vascular beds of specific organs, as well as several activators and repressors that participate in its cell type and organ-specific regulation of transcription.We have identified regions of the VWF promoter that target its activation specifically to brain and lung endothelial cells.additionally we demonstrated that two transacting factors, namely NFIB and YY1 specifically participate in VWF transcriptional activation in lung.VWF expression in lung is predominantly detected in larger vessels with low or non-detectable levels in the capillaries.Diseases that target vasculature of distinct organs,such as lung vasculature in pulmonary hypertension, are associated with changes in the levels of circulating VWF,while the mechanism of this increased plasma VWF is not determined.We have generated transgenic mice expressing LacZ gene under the regulation ofVWF gene sequences that target expression to brain and lung vasculature exclusively and exposed these mice to hypoxia as model of pulmonary hypertension.Analyses of endogenous VWF and LacZ transgene expression in hypoxia treated mice compared to control demonstrated that upregulation of VWF promoter activity as well as its de novo activation in microvasculature of lung, suggesting a phenotypic shift from anticoagulant to procoagulant activity in microvascular EC of the lung.Furthermore, we demonstrated that this process was associated with modulation of NFIB and YY1 activities.