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The promotion of endothelial cell attachment and spreading using FNIII10 fused to VEGF-A165

Paper ID Volume ID Publish Year Pages File Format Full-Text
6519 494 2013 11 PDF Available
Title
The promotion of endothelial cell attachment and spreading using FNIII10 fused to VEGF-A165
Abstract

Synergy in the downstream signaling pathways of the vascular endothelial growth factor receptor-2 (VEGFR-2) and the integrin αvβ3 is critical for blood vessel formation. Thus, agents that activate both receptors could possess efficient pro-angiogenic potential. Here, we created a fibrin-binding bi-functional protein (FNIII10-VEGF) consisting of the 10th type III domain of fibronectin (FNIII10) fused to a plasmin-resistant VEGF-A165 mutant (VEGF) that potentiated angiogenic processes when compared to the effect of the separate molecules. FNIII10-VEGF was able to bind both VEGFR-2 and integrin αvβ3. Intriguingly, cell attachment and spreading to immobilized FNIII10-VEGF was significantly enhanced compared to individual FNIII10 or VEGF proteins. Delivery of immobilized FNIII10-VEGF by covalent linkage to a fibrin matrix significantly enhanced the angiogenic response in an in vivo wound healing assay compared to soluble VEGF. Unexpectedly, the angiogenic response to fibrin-immobilized FNIII10-VEGF was reduced in comparison to the pro-angiogenic effect of fibrin-immobilized VEGF. Collectively, findings of this study corroborate a critical role for a subtle balance of the integrin-VEGF interplay in angiogenesis and provide insight in how engineered growth factors in concert with biomaterial matrices may offer a potent molecular/material approach to harness these interactions for therapeutic angiogenesis.

Keywords
Angiogenesis; VEGF; Fibronectin; Integrins; Adhesion; Cell spreading
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The promotion of endothelial cell attachment and spreading using FNIII10 fused to VEGF-A165
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 24, August 2013, Pages 5958–5968
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us