Insulin-like Growth Factor 1 (IGF-1) Stabilizes Nascent Blood Vessels

Abstract Herein we report that VEGF-A and IGF-1 differ in their ability to stabilize newly formed blood vessels and endothelial cell tubes. Whereas VEGF-A failed to support an enduring vascular response, IGF-1 stabilized neovessels generated from primary endothelial cells derived from various vascular beds and mouse retinal explants. In these experimental systems, destabilization/regression was driven by lysophosphatidic acid (LPA). Because previous studies established that Erk antagonizes LPA-mediated regression, we considered if Erk was an essential component of IGF-dependent stabilization. Indeed, IGF-1 lost its ability to stabilize neovessels when the Erk pathway was pharmacologically inhibited. Furthermore, stabilization was associated with prolonged Erk activity; in the presence of IGF-1, Erk activity persisted longer than in the presence of VEGF or LPA alone. These studies reveal that VEGF and IGF-1 can have distinct inputs in the angiogenic process; in contrast to VEGF, IGF-1 stabilizes neovessels, which was dependent on Erk activity and associated with prolonged activation.