Angiogenic peptides improve blood flow and promote capillary growth in a diabetic and ischaemic mouse model.
OBJECTIVE
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.


METHODS
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.
Felsenstein Medical Research Center, Tel-Aviv University Sackler School of Medicine, Rabin Medical Center, Beilinson Campus, Petah Tikva 49100, Israel.
A
A
Raiter
Z
Z
Bechor
M
M
Kleiman
D
D
Leshem-Lev
A
A
Battler
B
B
Hardy
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D002196:Capillaries / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D015687:Cell Hypoxia; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003097:Collateral Circulation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006614:Hindlimb; D006801:Humans; D007511:Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors
D043925:Angiogenesis Inducing Agents; D001786:Blood Glucose; D010455:Peptides