Angiopoietin-1, but not Platelet-Derived Growth Factor-AB, Is a Cooperative Stimulator of Vascular Endothelial Growth Factor A-Accelerated Endothelial Cell Scratch Closure

Wound healing and the grow-in of free tissue grafts critically depend on blood vessel growth, i.e., on the angiogenic invasion of endothelial cells, which is critically reduced in smokers, in patients suffering from microangiopathies (e.g., in diabetes), or in those who are treated with immunosuppressives. Although several angiogenic factors have been tested to accelerate wound healing in such critically patients, their combinations have not yet been systematically investigated. This study was done to reveal which combination of proangiogenic with promaturating factors is the most effective in an endothelial wound closure assay. Human umbilical vein endothelial cells were isolated, cultured to confluence, and subjected to a scratch wound assay with the addition of vascular endothelial growth factor (VEGF)-A165, platelet-derived growth factor (PDGF)-AB, angiopoietin-1 (ANG1), or ANG2 and all of their 16 possible combinations. VEGF-A165 plus ANG1 was most effective at accelerating endothelial scratch closure. Moreover, VEGF-A165 stimulated wound closure in all combinations tested, while it was attenuated by PDGF-AB. Thus, with respect to their effects on endothelial cells, a combination of VEGF-A with ANG1 is the most promising and is superior to combinations with PDGF-AB.