The concomitant presence of the fibrin fragment Bbeta15-42 competed with E1 framents for binding to VEcadherin thereby reduced leukocyte transmigration. Here we show that FX06 is also a signaling molecule. It antagonizes RhoA activation in vitro and reduces vascular leak in vivo. As reviewed recently by Vestweber mechanisms of leukocyte transmigration and vascular GSK2118436 permeability are tightly linked and strongly influenced by VE-cadherin functions. Previously we proposed a graphical systems biology approach, causal mapping , to describe complex cellular and molecular systems. CMAP is a course-grained biological network tool that takes into account causal interactions between network elements and provides a description of the overall system dynamics. The network of interest is modeled as a map based on known and hypothetical interactions between elements of the system, in a manner similar to common portrayals of signaling pathways. CMAP provides an intuitive algorithm for evolving the values of the elements in time based on the interactions between the elements. The CMAP maintains the simplicity of other coursegrained methods, including Boolean networks, but there are essential differences. The elements of the CMAP, which are referred to as concepts, vary continuously in time between the values of 0 and 1. VE-cadherin is a transmembrane molecule crucially involved in the regulation of endothelial barrier function and RhoA activity. FAK reorganisation, actin stress fiber formation and RhoA activation are established signs of stress-induced vascular hyperpermeability. VE-cadherin is organized in a multimeric protein complex called adherens junction. Both, the phosphorylation status of VEcadherin and the composition of this protein complex are altered in response to factors interfering with vascular barrier function. There is increasing recognition that lesion composition rather than size determines the acute complications of atherosclerotic disease in humans. Several studies suggested that thin-cap fibroatheroma are prone to rupture and result in acute coronary artery occlusions , whereas obstructive, calcified plaques result in clinically stable angina pectoris. Initiation and progression of the atherosclerotic lesion are highly complex processes, and many aspects of atherogenesis remain incompletely understood. Ectopic visceral adipose tissue was linked to the pathogenesis of atherosclerosis due to secretion of a multitude of pro- and anti-atherogenic cytokines and adipokines. Among proteins known to be associated with cadherins are catenins, VE-PTP, p120cat, c-src, csk or Fyn. Thus, in a next step we analyzed whether FX06 altered the composition of the VEcadherin complex. Among proteins co-precipitated with VEcadherin, only Fyn was significantly affected. The addition of FX06 to endothelial cells caused an immediate dissociation of Fyn from VE-cadherin. Fyn is a broadly expressed regulatory src kinase. But again the knowledge about the functional differences of the specific transcripts is still limited.