Fiedler Ulrike, Augustin Hellmut G
Department of Vascular Biology and Angiogenesis Research, Tumor Biology Center, Freiburg 79106, Germany.
Trends Immunol. 2006 Dec;27(12):552-8. doi: 10.1016/j.it.2006.10.004. Epub 2006 Oct 12.
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.
血管生成素（Ang）-Tie配体-受体系统在调节血管完整性和静止状态方面具有关键的调控作用。除了在血管生成中的作用外，它还是包括炎症在内的多种疾病的重要调节因子。Ang-1介导的Tie2激活是维持内皮细胞静止状态所必需的。激动性的Ang-1功能被Ang-2拮抗，据信Ang-2会抑制Ang-1-Tie2信号传导。Ang-2会破坏静止的内皮细胞稳定性，并使其对外部刺激产生反应，从而促进炎症（肿瘤坏死因子和白细胞介素-1）和血管生成（血管内皮生长因子）细胞因子的活性。有趣的是，静止的内皮细胞弱表达Ang-2，但在内皮细胞激活后会强烈上调。此外，内皮细胞将Ang-2储存在魏尔-帕拉德小体中，刺激后可迅速释放，这表明Ang-2在控制快速血管适应性过程中发挥作用。这表明Ang-2是Ang-Tie2轴的动态调节因子，从而作为一个内置开关控制静止的内皮细胞向激活的反应性内皮细胞的转变。
