The pathways of VWF secretion and their polarity. Diagram of a blood vessel showing the relative amount (length of arrows) and direction of secreted VWF from the 3 different secretory pathways from endothelial cells. The direction of VWF secreted either to the apical (vessel lumen) or the basolateral side (subendothelial matrix) of endothelial cells from each pathway is indicated by the direction of the arrows. Release from the constitutive pathway, which is Brefeldin A–sensitive, is exclusively to the basolateral side of endothelial cells, and is mostly composed of LMW-VWF multimers. Basal VWF release, the continuous release from WPBs, occurs mostly toward the apical side of endothelial cells, with a small amount secreted basolaterally, and is composed of UL-VWF multimer together with a dimer band. Regulated release, originating from WPB after a secretagogue stimulant, occurs predominantly to the apical side, with some release to the basolateral side, and is composed of exclusively UL-VWF multimers.