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

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 an...

Full description

Saved in:
Bibliographic Details
Published inThe Journal of biological chemistry Vol. 290; no. 10; pp. 6349 - 6360
Main Authors Jacobo, Sarah Melissa P., Kazlauskas, Andrius
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 06.03.2015
American Society for Biochemistry and Molecular Biology
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary: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. Background: Although both VEGF-A and IGF-1 promote angiogenesis, their relative contribution to neovessel stability is not completely understood. Results: To generate stable tubes, VEGF-driven tube formation must be accompanied by IGF-1-mediated stabilization. The mechanism involves IGF-1-mediated prolonged activation of Erk, which antagonizes LPA-driven regression. Conclusion: IGF-1 stabilizes VEGF-A-driven tube formation. Significance: Anti-VEGF therapy can be complemented by approaches that modulate Erk or LPA pathways.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M114.634154