title: Experimental research on therapeutic angiogenesis induced by hepatocyte growth factor directed by ultrasound-targeted microbubble destruction in rats.
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.
authors.affiliation: Institute of Ultrasound Imaging, Chongqing University of Medical Sciences, 74 Linjiang Rd, Yuzhong, 400010 Chongqing, China.
authors.forename: Xingsheng
authors.initials: X
authors.lastname: Li
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.forename: Haitao
authors.initials: H
authors.lastname: Ran
authors.forename: Xuelin
authors.initials: X
authors.lastname: Li
authors.forename: Qiaoying
authors.initials: Q
authors.lastname: Yuan
authors.forename: Yuanyi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Jianli
authors.initials: J
authors.lastname: Ren
authors.forename: Lin
authors.initials: L
authors.lastname: Su
authors.forename: Wenfang
authors.initials: W
authors.lastname: Zhang
authors.forename: Qiao
authors.initials: Q
authors.lastname: Li
authors.forename: Chuanshan
authors.initials: C
authors.lastname: Xu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D007150:Immunohistochemistry; D045423:Microbubbles; D009203:Myocardial Infarction / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014465:Ultrasonics; D020257:Ventricular Remodeling
chemical_list: D017228:Hepatocyte Growth Factor