Abstract 17686: Syndecan-4 Proteoliposomes Enhance FGF-2 Induced Proliferation, Migration and Neovascularization of Ischemic Muscle
Objectives: Inducing angiogenesis for the treatment of ischemia is an appealing therapeutic strategy for patients in whom traditional treatment modalities cannot be performed or are ineffective. While therapeutic angiogenesis holds great promise for treating patients with ischemia, none of the current methods has found success in clinical trials.
Methods: Here, we developed a novel method for improving the biological activity of FGF-2 by co-delivering the growth factor with a liposomally embedded co-receptor, syndecan-4. We compared this method of growth factor delivery to FGF-2 alone in in-vitro experiments using a wound healing assay of cell migration, thymidine incorporation for proliferation and a tube formation assay for angiogenic differentiation. We also created hind limb ischemia in rats through femoral artery ligation. Following induction of ischemia, we delivered FGF-2, control or FGF-2 and syndecan-4 proteoliposomes to the rats using an osmotic pump and measure revascularization by Laser Doppler imaging, microCT and histological analysis.
Results: Syndecan-4 proteoliposomes significantly increased endothelial cell growth, migration and tube formation. In-vivo treatment of rats with hind limb ischemia demonstrated increased revascularization in response to FGF-2 with co-delivery of syndecan-4 proteoliposomes. Laser Doppler imaging (A) showed that syndecan-4 proteoliposomes lead to a nearly complete resolution of ischemia by 7 days whereas FGF-2 alone did not resolve the ischemia by 16 days of treatment (B). This result was confirmed by histological analysis (C) and microCT based arterial reconstruction.
Conclusion: Taken together, these results support that liposomal delivery of syndecan-4 is an effective means to improving the therapeutic potential of using growth factors to achieve therapeutic neovascularization of ischemic tissue.
- Peripheral arterial disease
- Ischemic heart disease
- Cardiovascular therapeutics
- © 2011 by American Heart Association, Inc.