Myocardial angiogenesis after plasmid or adenoviral VEGF-A(165) gene transfer in rat myocardial infarction model.
OBJECTIVE
To compare gene transfer of plasmid (P) and adenovirus (Ad) encoding human vascular endothelial growth factor-A165 (hVEGF-A165) angiogenic efficacy and adverse effects as regards apoptosis and ectopic expression of the transgene in a rat myocardial infarction model.


METHODS
Myocardial infarction was provoked in Fisher rats. One week later, PhVEGF-A165, PLacZ, AdhVEGF-A165, or AdLacZ was transferred intramyocardially along the border of the myocardial infarction. hVEGF-A expression was detected with ELISA. Myocardial vessel density was analyzed 1 and 4 weeks after gene transfer. Apoptosis was detected by TUNEL staining. Cardiac function was assessed with Tissue Doppler Velocity Imaging.


RESULTS
Although AdhVEGF-A165 had substantially higher myocardial hVEGF-A expression than PhVEGF-A165, AdhVEGF-A165 and PhVEGF-A165 induced angiogenic effects to a similar extent with maintained increased arteriolar density after 4 weeks of gene transfer (p < 0.05). The two treatments also improved left ventricular function similarly. Adenoviral gene transfer induced a higher number of TUNEL positive cells than plasmid (p < 0.02). Ectopic expression of the transgene was present with both vectors but substantially higher after adenoviral gene transfer.


CONCLUSIONS
AdhVEGF-A165 has no obvious angiogenic advantage over PhVEGF-A165 but more side effects at least in a rat myocardial infarction model. This indicates that PhVEGF-A165 might be more applicable for therapeutic angiogenesis than AdhVEGF-A165.
Hao
Xiaojin
X
Department of Cardiology, Karolinska University Hospital, M52, S-141 86, Stockholm, Sweden.
Månsson-Broberg
Agneta
A
Grinnemo
Karl-Henrik
KH
Siddiqui
Anwar J
AJ
Dellgren
Göran
G
Brodin
Lars A
LA
Sylvén
Christer
C
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D001160:Arterioles; D003331:Coronary Vessels; D004247:DNA / Q000008:administration & dosage; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015870:Gene Expression; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D020287:In Situ Nick-End Labeling; D007267:Injections; D007763:Lac Operon; D017078:Laser-Doppler Flowmetry; D008297:Male; D023421:Models, Animal; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic; D010446:Peptide Fragments; D051381:Rats; D011916:Rats, Inbred F344; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D012039:Regional Blood Flow; D014161:Transduction, Genetic / Q000379:methods; D014162:Transfection / Q000379:methods; D019076:Transgenes; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D004247:DNA