Weibel-Palade Bodies (WPBs) are endothelial-specific secretory granules. WPBs store von Willebrand Factor (vWF), a glycoprotein central to haemostasis and whose dysregulation is associated with a host of pathologies with thrombotic phenotypes. WPBs have a peculiar cylindrical shape, with lengths varying between 0.5 and 5 micrometers. I have recently shown that the size of WPBs depends on the structural status of the Golgi apparatus. When the Golgi is highly connected forming the architecture known as “ribbon”, WPBs of all sizes are generated. When the Golgi is fragmented, only short WPBs are made by cells. WPB size is of consequence for the activity of its vWF cargo. vWF secreted from short WPBs shows reduced capability of recruiting platelets and the soluble pool of vWF present in circulating plasma, suggesting that the size of WPBs represents a control node for the haemostatic activity and/or thrombotic propensity of endothelial cells.
These findings have prompted the project I am currently leading, which involves screening of compounds in search of modulators of WPB size, with the aim of identifying molecules with promising anti-thrombotic activity for clinical applications.