title: Insulin-like growth factor 1 (IGF-1) stabilizes nascent blood vessels.
abstract: Here we report that VEGF-A and IGF-1 differ in their ability to stabilize newly formed blood vessels and endothelial cell tubes. Although 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 have established that Erk antagonizes LPA-mediated regression, we considered whether Erk was an essential component of IGF-dependent stabilization. Indeed, IGF-1 lost its ability to stabilize neovessels when the Erk pathway was inhibited pharmacologically. 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 is dependent on Erk activity and associated with prolonged activation.
authors.affiliation: From the Department of Ophthalmology, Harvard Medical School, The Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02115.
authors.forename: Sarah Melissa P
authors.initials: SM
authors.lastname: Jacobo
authors.affiliation: From the Department of Ophthalmology, Harvard Medical School, The Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02115 andrius_kazlauskas@meei.harvard.edu.
authors.forename: Andrius
authors.initials: A
authors.lastname: Kazlauskas
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000254:growth & development* / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D004730:Endothelium, Vascular / Q000254:growth & development / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008246:Lysophospholipids / Q000008:administration & dosage; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D018919:Neovascularization, Physiologic; D012171:Retinal Vessels / Q000254:growth & development / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D008246:Lysophospholipids; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D007334:Insulin-Like Growth Factor I; C032881:lysophosphatidic acid
keywords: Angiogenesis; Cell Migration; Insulin-like Growth Factor (IGF); LPA; VEGF; Vascular Biology