Visit our Expo - Redox and Inflammation signaling 2012

Session XI: Cell death and cardiovascular diseases Poster XI, 10
RoY a Novel Synthetic Peptide with Angiogenic and anti Apoptotic properties
1Annat Raiter, 1 Chana Weiss, 1 Orly Kudasi, 2Alexander Battler and 1 Britta Hardy.
1Felsenstein Medical Research Center, Tel-Aviv University School of Medicine,
2Cardiology Dept., Rabin Medical Center, Petah-Tikva, Israel.
Email: bhardy@post.tau.ac.il
Background: We have identified a novel 12 amino-acid synthetic peptide, RoY, selected
from a phage display peptide library by screening against endothelial cells under hypoxia.
RoY peptide specifically binds endothelial cells, induces angiogenesis in vitro manifested by
proliferation, migration and tube formation.
Objectives: to evaluate the therapeutic potential of the synthetic RoY peptide in restoring
perfusion in a mouse hind limb ischemic model and to elucidate the mechanism of RoY
peptide angiogenic activity under hypoxia by gene expression.
Results: Ischemia was created by ligation and excision of the femoral artery in one hind limb
of C57BL mice. Seven days after operation, perfusion in the ischemic leg was reduced to
50% in control PBS group, to 65% in RoY peptide group and to 70% in the VEGF group.
However, while RoY peptide increased perfusion to 99% at 21 days, perfusion was reduced to
80% with VEGF and remained unchanged with PBS. Gene array, confirmed by RT-PCR,
revealed up-regulation of angiogenesis growth factors Angiopoitin-2 and bFGF, Upregulation
of chemokine CCL20 and of the anti-apoptotic gene TNF-RSF10D. In contrast,
VEGF gene expression in endothelial cells incubated with RoY peptide for 3 or 24 hours was
not up-regulated. The percent of apoptosis, measured by FACS analysis, of endothelial cells
incubated under hypoxic conditions was inhibited by the addition of RoY peptide from 62%
to 33%.
Conclusion: RoY is a synthetic peptide that exhibits angiogenic and anti-apoptotic properties
under hypoxia by up regulation of growth factors, cytokines and anti apoptotic genes. RoY
peptide activity is VEGF independent thus suggests a way to bypass classical VEGF
angiogenic system. Treatment of ischemic leg with RoY peptide improved perfusion and
walking and climbing function in the mouse. This novel peptide with pro-angiogenic
properties may be used as a new therapeutic modality to hypo-vascular diseases.
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