A Raiter1, Z Bechor, M Kleiman, D Leshem-Lev, A Battler, B Hardy. 1. Felsenstein Medical Research Center, Tel-Aviv University Sackler School of Medicine, Rabin Medical Center, Beilinson Campus, Petah Tikva 49100, Israel.
Abstract
OBJECTIVES: It is a common clinical observation that collateral vessel development is impaired in diabetic patients with ischaemic vascular diseases. Consequently, alternative revascularisation strategies in diabetic patients are needed. This study presents the effect and mechanism of new peptide therapeutic angiogenesis in an ischaemic and diabetic mouse model. DESIGN: Streptozocin-injected mice that had undergone hind-limb ischaemia were treated with angiogenic peptides. Blood flow restoration was calculated by laser Doppler imager and corroborated by histological section. For the mechanism study, endothelial cells were exposed to hypoxia and high glucose concentrations to study the effect of the peptides on proliferation and anti-apoptosis. RESULTS: The peptides significantly restored blood perfusion 21 days after surgery in the diabetic mice (p < 0.01) by neo-vascularisation, corroborated by an increase in capillary density. In addition, the peptides induced the proliferation of hypoxic endothelial cells (p < 0.01) and protected the cells from apoptosis in high glucose cultures. CONCLUSIONS: This is the first approach for treatment of ischaemic vascular disease with peptides in a diabetic mouse model. Copyright 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
OBJECTIVES: It is a common clinical observation that collateral vessel development is impaired in diabeticpatients with ischaemic vascular diseases. Consequently, alternative revascularisation strategies in diabeticpatients are needed. This study presents the effect and mechanism of new peptide therapeutic angiogenesis in an ischaemic and diabeticmouse model. DESIGN: Streptozocin-injected mice that had undergone hind-limb ischaemia were treated with angiogenic peptides. Blood flow restoration was calculated by laser Doppler imager and corroborated by histological section. For the mechanism study, endothelial cells were exposed to hypoxia and high glucose concentrations to study the effect of the peptides on proliferation and anti-apoptosis. RESULTS: The peptides significantly restored blood perfusion 21 days after surgery in the diabeticmice (p < 0.01) by neo-vascularisation, corroborated by an increase in capillary density. In addition, the peptides induced the proliferation of hypoxic endothelial cells (p < 0.01) and protected the cells from apoptosis in high glucose cultures. CONCLUSIONS: This is the first approach for treatment of ischaemic vascular disease with peptides in a diabeticmouse model. Copyright 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.