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Overcoming disease-induced growth factor resistance in therapeutic angiogenesis using recombinant co-receptors delivered by a liposomal system

Paper ID Volume ID Publish Year Pages File Format Full-Text
6209 468 2014 10 PDF Available
Title
Overcoming disease-induced growth factor resistance in therapeutic angiogenesis using recombinant co-receptors delivered by a liposomal system
Abstract

Current treatment options for ischemia include percutaneous interventions, surgical bypass or pharmacological interventions aimed at slowing the progression of vascular disease. Unfortunately, while each of these treatment modalities provides some benefit for patients in the short-term, many patients have resistant or recurrent disease that is poorly managed by these therapies. A highly appealing strategy for treating ischemic disease is to stimulate the revascularization of the tissue to restore blood flow. While many techniques have been explored in this regard, clinically effective angiogenic therapies remain elusive. Here, we hypothesized that the presence of co-morbid disease states inherently alters the ability of the body to respond to angiogenic therapies. Using a mouse model of diabetes and obesity, we examined alterations in the major components for the signaling pathways for FGF-2, VEGF-A and PDGF under normal and high fat dietary conditions. In skeletal muscle, a high fat diet increased levels of growth factor receptors and co-receptors including syndecan-1, syndecan-4 and PDGFR-α in wild-type mice. These increases did not occur in Ob/Ob mice on a high fat diet and there was a significant decrease in protein levels for neuropilin-1 and heparanase in these mice. With the aim of increasing growth factor effectiveness in the context of disease, we examined whether local treatment with alginate gel-delivered FGF-2 and syndecan-4 proteoliposomes could overcome the growth factor resistance in these mice. This treatment enhanced the formation of new blood vessels in Ob/Ob mice by 6 fold in comparison to FGF-2 delivered alone. Our studies support that disease states cause a profound shift in growth factor signaling pathways and that co-receptor-based therapies have potential to overcome growth factor resistance in the context of disease.

Keywords
Angiogenesis; Neovascularization; Ischemia; Fibroblast growth factor-2 (FGF-2); Syndecan-4 proteoliposomes; Peripheral arterial disease
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Overcoming disease-induced growth factor resistance in therapeutic angiogenesis using recombinant co-receptors delivered by a liposomal system
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 35, Issue 1, January 2014, Pages 196–205
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