We generated a novel nanoparticle called PVAX, which has intrinsic anti-apoptotic and anti-inflammatory properties. This nanoparticle was loaded with Neuropeptide Y3-36, an angiogenic neuro-hormone that plays a central role in angiogenesis. Subsequently, we investigated whether PVAX-NPY3-36 could act as a therapeutic agent and induce angiogenesis and vascular remodeling in a murine model of hind limb ischemia. Adult C57BL/J6 mice (n=40) were assigned to treatment groups: Control, Ischemia PBS, Ischemia PVAX, Ischemia NPY3-36, and Ischemia PVAX-NPY3-36. Ischemia was induced by ligation of the femoral artery in all groups except Control and given relevant treatments (PBS, PVAX, NPY3-36, and PVAX-NPY3-36). Blood flow was quantified using laser Doppler imaging. On days 3 and 14 post-treatment, mice were euthanized to harvest gastrocnemius muscle for immunohistochemistry and immunoblotting. Blood flow was significantly improved in the PVAX-NPY3-36 group after 14 days. Western blot showed an increase in angiogenic factors VEGF-R2 and PDGF-β (p=0.0035 and p=0.031, respectively) and anti-apoptotic marker Bcl-2 in the PVAX-NPY3-36 group as compared to Ischemia PBS group (p=0.023). Pro-apoptotic marker Smad5 was significantly decreased in the PVAX-NPY3-36 group as compared to the Ischemia PBS group (p=0.028). Furthermore, Y2 receptors were visualized in endothelial cells of newly formed arteries in the PVAX-NPY3-36 group. In conclusion, we were able to show that PVAX-NPY3-36 can induce angiogenesis and arteriogenesis as well as improve functional blood flow in a murine model of hind limb ischemia.
- PVAX nanoparticle
- hind limb ishemia
- functional blood flow
- Copyright © 2016, Journal of Applied Physiology