By combining different mouse models with state of the art imaging and protein detection methods, we
will verify the in vivo relevance of the CD154-induced ultra-large von Willebrand factor (ULVWF) multimer-
mediated endothelial cell-platelet-monocyte/macrophage crosstalk in adaptive and maladaptive
vascular remodeling processes. We will further detail the conditions favoring deposition of these
ULVWF strings on the endothelial cell surface, and explore the impact of a genetic defect in endothelial
cell nitric oxide formation on this multicellular crosstalk orchestrated through repeated CD40-CD154 costimulation.