Delivery of high dose VEGF plasmid using fibrin carrier does not influence its angiogenic potency.
Delivery of DNA mixed with a degradable matrix carrier was supposed to improve transgene expression. Using a rabbit hind-limb ischemia model, we tested the angiogenic potency of plasmid encoding human vascular endothelial growth factor (pSG5-VEGF165) entrapped in fibrin sealant. Animals were injected intramuscularly with 500 microg of pSG5-VEGF165 or control plasmid, dissolved in saline (PBS) or fibrin glue. After 14 days, presence of delivered constructs and expression of transgene was confirmed in injected muscles of all animals. There were no significant differences in the levels of human VEGF mRNA and protein between VEGF-PBS and VEGF-fibrin groups (Mann-Whitney test). Accordingly, pSG5-VEGF165 regardless of the way of delivery, induced similar increases in capillary density within treated muscles (ANOVA). Control plasmid did not show any effects. In conclusion, injection of pSG5-VEGF165 into ischemic adductor muscle leads to synthesis of human VEGF and increases the number of capillaries. Fibrin carrier does not influence its angiogenic potential.
Jozkowicz
A
A
Department of Vascular Surgery, University of Vienna, Vienna, Austria. alicia@mol.uj.edu.pl
Fügl
A
A
Nanobashvili
J
J
Neumayer
C
C
Dulak
J
J
Valentini
D
D
Funovics
P
P
Polterauer
P
P
Redl
H
H
Huk
I
I
D000818:Animals; D016228:Endothelial Growth Factors / Q000008:administration & dosage* / Q000235:genetics* / Q000276:immunology; D005260:Female; D015718:Fibrin Tissue Adhesive / Q000008:administration & dosage* / Q000276:immunology; D015870:Gene Expression / Q000235:genetics; D015316:Genetic Therapy; D006614:Hindlimb; D007109:Immunity / Q000187:drug effects / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000235:genetics* / Q000276:immunology; D007511:Ischemia / Q000628:therapy*; D008222:Lymphokines / Q000008:administration & dosage* / Q000235:genetics* / Q000276:immunology; D008297:Male; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000098:blood supply*; D018919:Neovascularization, Physiologic / Q000235:genetics* / Q000502:physiology; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D011817:Rabbits; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D015718:Fibrin Tissue Adhesive; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors