Tuning the SNAREs that regulate Weibel-Palade body exocytosis

Endothelial cells form the inner lining of the vessel wall and provide a barrier between circulating blood and the underlying tissue. The endothelium participates in maintenance of vascular homeostasis and facilitates rapid responses to environmental changes such as inflammation or vascular damage. A cocktail of bioactive components participating in these processes are stored in endothelial-specific storage organelles, designated Weibel-Palade bodies (WPBs). The main component of WPBs is von Willebrand factor (VWF). VWF functions in arrest of bleeding by capturing platelets thereby promoting thrombus formation at sites of vascular injury. Furthermore, VWF acts as a carrier for coagulation factor VIII. Several other mediators of hemostasis, inflammation and angiogenesis are co-stored with VWF in WPBs and are secreted into the vascular lumen upon WPB exocytosis. In this thesis we aim to obtain a better understanding of the composition of WPBs and the molecular mechanisms that regulate the release of WPB components into the bloodstream.