Role of Angiopoietin/Tie2 in Critical Illness: Promising Biomarker, Disease Mediator, and Therapeutic Target?

Figure 1

Scheme of the endothelial angiopoietin (Angpt)/Tie2 system highlighting fundamental signalling pathways. Angpt-1 ligation phosphorylates and thereby activates the Tie2 receptor promoting an anti-inflammatory signal via inhibition of surface adhesion molecule expression and the transcription factor NfkB. Moreover, the PI3K/Akt pathway promotes an antiapoptotic, prosurvival signal. The antipermeability effects are induced by maintaining the cytoskeletal architecture in a cortical quiescent formation. On a signalling level this is achieved by simultaneous inhibition of the Rho kinase and activation of the small GTPase Rac1 via IQGAP1 binding. Direct effects on the adherens junction protein VE-cadherin via src have also been reported. Upon stimulation, endothelial cells release prestored Angpt-2 from Weibel Palade bodies into the circulation. Angpt-2 competitively antagonizes positive Angpt-1/Tie2 signalling, thus dramatically activating the endothelial cell and priming it for further inflammatory stimuli.