Angiopoietins: a link between angiogenesis and inflammation.
The angiopoietin (Ang)-Tie ligand-receptor system has a key regulatory role in regulating vascular integrity and quiescence. Besides its role in angiogenesis, it is an important regulator in numerous diseases including inflammation. Ang-1-mediated Tie2 activation is required to maintain the quiescent resting state of the endothelium. Agonistic Ang-1 functions are antagonized by Ang-2, which is believed to inhibit Ang-1-Tie2 signaling. Ang-2 destabilizes the quiescent endothelium and primes it to respond to exogenous stimuli, thereby facilitating the activities of inflammatory (tumor necrosis factor and interleukin-1) and angiogenic (vascular endothelial growth factor) cytokines. Intriguingly, Ang-2 is expressed weakly by the resting endothelium but becomes strongly upregulated following endothelial activation. Moreover, endothelial cells store Ang-2 in Weibel-Palade bodies from where it can be made available quickly following stimulation, suggesting a role of Ang-2 in controlling rapid vascular adaptive processes. This suggests that Ang-2 is the dynamic regulator of the Ang-Tie2 axis, thereby functioning as a built-in switch controlling the transition of the resting quiescent endothelium towards the activated responsive endothelium.
Fiedler
Ulrike
U
Department of Vascular Biology and Angiogenesis Research, Tumor Biology Center, Freiburg 79106, Germany.
Augustin
Hellmut G
HG
D042702:Angiopoietin-2 / Q000502:physiology; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D018919:Neovascularization, Physiologic; D042764:Receptors, TIE / Q000378:metabolism
D042702:Angiopoietin-2; D042682:Angiopoietins; D042764:Receptors, TIE