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...
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Published in | The Journal of biological chemistry Vol. 290; no. 10; pp. 6349 - 6360 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
06.03.2015
American Society for Biochemistry and Molecular Biology |
Subjects | |
Online Access | Get full text |
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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. |
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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 |