Exocytosis of WPB of BOECs. BOECs were cultured in 12-well plates until confluent and then rinsed and incubated for 60 minutes at 37°C with release medium in the absence (Control) or presence (PMA) of 160 nM PMA, 100 μM histamine (Histamine), or 10 μM epinephrine plus 100 μM IBMX (Epinephrine). Each bar represents the percentage of secreted VWFpp as a fraction of total VWFpp (medium plus lysate) by 3 different passages of BOECs (between passages 4 and 8). (A) Regulated secretion of VWFpp from BOECs of a single representative healthy donor. Mean ± SD indicates variation of VWFpp secretion between 3 passages of BOECs. (B-D) Regulated secretion of VWFpp induced by PMA, histamine, or epinephrine was compared between BOECs derived from healthy donors (mean, 5 donors) and 5 participants heterozygous for a given VWF mutation. Mean ± SD indicates variation of VWFpp secretion between 3 passages of a single clone of BOECs (clone A for healthy donor 2 and clone A for donor 5, as presented in supplemental Figure 3). The bars for healthy donors in (B-D) were generated by pooling data from 5 healthy donors. In this case, the error bars indicate SD between the 5 healthy donors. The different responses to the indicated stimuli between patients and healthy donors were statistically analyzed using 1-way ANOVA with the Bonferroni post test. **P < .01; ***P < .001; ns, difference is statistically not significant.