Experimental research on therapeutic angiogenesis induced by hepatocyte growth factor directed by ultrasound-targeted microbubble destruction in rats.
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| Abstract | OBJECTIVE: The purpose of this study was to explore the feasibility of therapeutic angiogenesis in myocardial infarction induced by hepatocyte growth factor (HGF) mediated by ultrasound-targeted microbubble destruction. METHODS: Forty Wistar rats were divided into 4 groups after the models of myocardial infarction were prepared: (1) HGF, ultrasound, and microbubbles (HGF+US/MB), (2) HGF and ultrasound, (3) HGF and microbubbles, and (4) surgery alone. Destruction of ultrasound-targeted microbubbles loaded with the HGF gene with an electrocardiographic trigger mode was performed in the HGF+US/MB group. All the rats were killed after being transfected for 14 days. Enhanced green fluorescent protein expression was examined in the myocardium, liver, and kidney in all groups by fluorescence microscopy; CD34 expression was detected by immunohistochemistry, and microvessel density (MVD) was counted in the high-power field on microscopy. Hepatocyte growth factor expression in the myocardium was detected by western blotting and an enzyme-linked immunosorbent assay. RESULTS:
Enhanced green fluorescent protein expression was detected in the myocardium of the HGF+US/MB group, but a few areas of HGF expression were detected only in small vessels and the capillary endothelium, and no expression was found in the surgery-alone and HGF and microbubbles groups. The results of MVD counting by microscopy showed that the MVD in the myocardium of the HGF+US/MB group was the highest among all the groups. The results of western blotting and the enzyme-linked immunosorbent assay showed that the amount of HGF in the myocardium was highest in the HGF+US/MB group. CONCLUSIONS: Ultrasound-targeted microbubble destruction could deliver HGF into the infracted myocardium and produce an angiogenesis effect, which could provide a novel strategy for gene therapy of myocardial infarction.
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| Authors | Xingsheng Li, Zhigang Wang, Haitao Ran, Xuelin Li, Qiaoying Yuan, Yuanyi Zheng, Jianli Ren, Lin Su, Wenfang Zhang, Qiao Li, Chuanshan Xu |
| Journal | Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine (J Ultrasound Med) Vol. 27 Issue 3 Pg. 453-60 (Mar 2008) ISSN: 0278-4297 [Print] England |
| PMID | 18314523 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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