Circulating levels of components of the Ang/Tie system have been measured in patients admitted to the critical care unit. In trauma patients plasma Ang-2, but not plasma Ang-1 or VEGF, was increased early after trauma, and the level correlated with disease severity and outcome [34] . In children with sepsis and septic shock, Ang-2 levels in plasma were increased and once again correlated with disease severity, whereas Ang-1 levels were decreased [35] . The same Ang-1/ Ang-2 pattern is seen in adults with sepsis [28, 29, [36] [37] [38] [39] . The results of studies of the Ang/Tie system in humans are summarized in Table 1 . In sepsis, VEGF and its soluble receptor sFLT-1 (soluble VEGFR-1) are also increased in a disease severity-dependent manner [40] [41] [42] .The picture that emerges from these studies is that the Ang/Tie signalling system appears to play a crucial role in the symptoms of MODS. Findings in animal models and in patients suggest that Ang-1 stabilizes ECs and Ang-2 prepares them for action. The close relation with VEGF is also apparent. four (Ang-1) and two (Ang-2) subunits [48, 49] . The dissimilarity between Ang-1 and Ang-2 signalling lies in subtle differences in the receptor binding domain that lead to distinct intracellular actions of the receptor; differential cellular handling of both receptor and ligands after binding and signalling initiation may also play a role [49, 50] .