Myocardial angiogenesis after plasmid or adenoviral VEGF-A₁₆₅ gene transfer in rat myocardial infarction model

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• 作者：Xiaojin Hao ; Agneta Må ; nsson-Broberg ; Karl-Henrik Grinnemo ; Anwar J. Siddiqui ; Gö ; ran Dellgren ; Lars Å ; . Brodin ; Christer Sylvé ; n
• 关键词：Angiogenesis ; Gene therapy ; Infarction ; Growth factors ; Apoptosis
• 刊名：Cardiovascular Research
• 出版年：2007
• 期刊代码：48_00086363
• 类别：med
• 出版时间：1 February 2007
• 卷：73
• 期：3
• 页码：481-487
• 文件大小：641 K

摘要

>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.