In the mature vessel, Ang-1 acts as a paracrine signal to maintain a quiescent status quo, whereas Ang-2 induces or facilitates an autocrine EC response [74, 153] . In general, Ang-1 can be viewed as a stabilizing messenger, causing continuous Tie2 phosphorylation, and Ang-2 as a destabilizing messenger preparing for action [17] . Attempts to unravel the exact molecular mechanisms that control the system are complicated by microenvironment-dependent endothelial phenotypes and reactivity and by flow typedependent reactions to dynamic changes [13, 154, 155] . Hence, the EC must be viewed in the context of its surroundings -the pericyte at the abluminal site, and the blood and its constituents on the luminal site [64] . The Ang/Tie system certainly functions as one of the junctions in signal transduction and plays a key role in multiple cellular processes, many of which have been linked to MODS.