Angiopoietin/Tie receptor system: emerging targets for therapeutic angiogenesis and anti-angiogenic therapy

Abstract

Balanced regulation of endothelial cell function and co-ordination of endothelial cells and periendothelial support cells by angiogenic growth factors and cell type-specific receptor tyrosine kinases is crucially involved in physiological angiogenesis. Disturbance of this fine-tuned balance is associated with disease-related neoangiogenesis, such as in tumour angiogenesis or in retinopathy, or in insufficient angiogenesis in occlusive vascular disease. In addition to the well known function of vascular endothelial growth factor (VEGF) as an endothelial cell-specific angiogenesis inducer and survival factor, recent studies on angiopoietins and their receptors have provided insight into the interplay of these endothelium-specific ligand-receptor systems in formation, maintenance and remodelling of the vasculature. Knowledge of the mechanisms by which these ligand-receptor systems are involved in regulation of the interaction of endothelial cells and their periendothelial support cells opens new opportunities for therapeutic angiogenesis to induce formation of functional blood vessels in occlusive disease, as well as to complement and/or enhance current anti-VEGF-based strategies for anti-angiogenic therapy.