| 19934363 |
Dong H, Wang Q, Zhang Y, Jiang B, Xu X, Zhang Z: Angiogenesis induced by hVEGF165 gene controlled by hypoxic response elements in rabbit ischemia myocardium. Exp Biol Med. 2009 Dec;234(12):1417-24.
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, declined, and approached pre-ischemia level at the end of 12 weeks of ischemia (P < 0.01). The significantly upregulated CD31 in hVEGF (165)-treated hearts presented from 8 to 12 weeks of ischemia compared with the control (P < 0.01). However, alpha-SMA expression was rapidly downregulated after ischemia and remained lower than the control level by the end of 12 weeks post-MI (P < 0.01). Overexpression of hVEGF (165) controlled by HIF-1alpha-HRE system shows a stably regional angiogenic efficacy in vivo. But, VEGF, as an early angiogenic cytokine, is inadequate for mediating histologically mature vessels in ischemia myocardium. |
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