In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 35, No. suppl_1 ( 2015-05)
Kurzfassung:
Previous research has attempted to use growth factor proteins and genes to revascularize ischemic tissues but none of the methods have found complete success in clinical trials. We have demonstrated the loss of co-receptors like syndecan-4 due to long-term diseased state and enhanced neovascularization of ischemic tissue due to co-delivery of syndesomes (syndecan-4 proteoliposomes) with FGF-2 in normal healthy rats. In this study, we used syndesomes to enhance revascularization in the ischemic hind limb of a growth factor resistant mouse model with diabetes, obesity and hyperlipidemia. We used ob/ob mice fed with high fat diet for 10 weeks. We induced ischemia through femoral artery ligation and implanted alginate beads containing treatments into the surgical site. The recovery of perfusion in the mice was tracked using laser speckle imaging. After 14 days, the ischemic limbs of the mice treated with FGF-2 with syndesomes had significantly higher perfusion compared to the FGF-2 alone group (A, B). Morphometric analysis on sections from the calf and thigh muscle of the mice demonstrated increased ischemic changes in the ischemic limbs of the FGF-2 alone group. Immunostaining for von Willebrand factor revealed increased neovascularization corresponding with the increase perfusion measured in the FGF-2 with syndesomes group (C, D). Immunostaining for pro-inflammatory M1 macrophage marker CD86 showed similar levels in both treatment groups (E, F). However, immunostaining for pro-wound healing M2 macrophage marker revealed significantly higher levels in the syndesome with FGF-2 treatment group (G, H). Taken together, these preliminary studies support that co-delivery of syndecan-4 with FGF-2 significantly enhances revascularization in the ischemic hind limb in a clinically relevant diseased mouse model. Our treatment restores the signaling pathway components that are lost due to diseased state causing tissues to become resistant to growth factor therapies.
Materialart:
Online-Ressource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.35.suppl_1.493
Sprache:
Englisch
Verlag:
Ovid Technologies (Wolters Kluwer Health)
Publikationsdatum:
2015
ZDB Id:
1494427-3
