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Myocardial angiogenesis after plasmid or adenoviral VEGF-A(165) gene transfer in rat myocardial infarction model
- Hao, Xiaojin (author)
-
- Mansson-Broberg, Agneta (author)
- Karolinska Institutet
-
- Grinnemo, Karl-Henrik (author)
- Karolinska Institutet
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- Dellgren, Goran (author)
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- (creator_code:org_t)
- Oxford University Press (OUP), 2007
- 2007
- English.
- In: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 73:3, s. 481-487
- Journal article (peer-reviewed)
Abstract
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- Objective: To compare gene transfer of plasmid (P) and adenovirus (Ad) encoding human vascular endothelial growth factor-A(165) (hVEGF-A(165)) 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-A(165), PLacZ, AdhVEGF-A(165), 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-A(165) had substantially higher myocardial hVEGF-A expression than PhVEGF-A(165), AdhVEGF-A(165) and PhVEGF-A(165) 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-A(165) might be more applicable for therapeutic angiogenesis than AdhVEGF-A(165).
Keyword
- angiogenesis
- gene therapy
- infarction
- growth factors
- apoptosis
- endothelial growth-factor
- expression
- ischemia
- vectors
- feasibility
- mechanisms
- apoptosis
- therapy
- artery
- trial
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- ref (subject category)
- art (subject category)
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