Angiopoietin signaling in the vasculature

• The angiopoietins and Tie receptors form an endothelial-specific signaling system.
• The Ang–Tie signaling system regulates blood and lymphatic vessel development.
• Ang1 stabilizes the matured blood vasculature and limits responses to injuries.
• Increased levels of Ang2 promote tumor angiogenesis, metastasis, and inflammation.
• Effective means to control Ang2 in inflammation and cancer should have clinical value.

The angiopoietin (Ang) growth factors and the endothelial Tie receptors regulate blood and lymphatic vessel development, and vascular permeability, inflammation, angiogenic remodeling and tumor vascularization in adult tissues. The angiopoietins activate the Tie receptors in unique in trans complexes at endothelial cell–cell and cell–matrix contacts. In addition, integrins have been implicated in the regulation of Ang–Tie signaling. Recent interest has focused on the function of angiopoietin-2 and its inhibition in the tumor vasculature and also in other pathological conditions associated with endothelial dysfunction. Here we review the current understanding of the signaling functions of the Ang–Tie pathway and its potential for future development of targeted vascular therapeutics.

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