Angiogenesis induced by hVEGF165 gene controlled by hypoxic response elements in rabbit ischemia myocardium
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Exp.Biol.Med.(Maywood.) 234 (12): 1417-1424 (2009)

Hypoxic response element (HRE) offers satisfactory control over expression of hVEGF(165) in cell levels. However, the characteristics of regenerated blood vessels induced by long-term expression of transferred hVEGF(165) under control of HRE in vivo remain unknown. This study aims to investigate the effect of HRE on control of long-term expression of rAAV-delivered hVEGF(165) gene to ischemic myocardium and evaluate characteristics of angiogenesis induced by hVEGF(165) in vivo. Rabbit ischemic heart models were established surgically, rAAV-9HRE-hVEGF(165) was transfected to ischemia hearts subjected to 12 week ischemia. Molecular biological and immunohistochemistry were employed to determine expressions of HIF-1alpha and hVEGF(165). Microvessel densities of CD31(+) and alpha-SMA(+) regenerated vessels were also evaluated. Expressions of both hVEGF(165) mRNA and protein were upregulated following over-expression of endogenous HIF-1alpha early after ischemia, peaked at 4-6 weeks post-MI,
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