[Therapeutic angiogenesis induced by hepatocyte growth factor directed by ultrasound-targeted microbubble destruction].
OBJECTIVE
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 established: HGF + ultrasound + microbubble (HGF + US/MB) groups, HGF and ultrasound (HGF + US) group, HGF and microbubble (HGF + MB) group, and surgery alone (SA) group. Ultrasound-targeted destruction microbubble loaded with HGF gene with ECG trigger was performed in HGF + US group. Microbubble loaded with HGF gene was infused intravenously in HGF + MB group, and normal saline were infused in SA group. All rats were killed 14 days after transfection. The CD34 expression was detected by immunohistochemistry (IHC), and microvessel density (MVD) was counted in high power field. The HGF expression on myocardium was detected by ELISA, and the correlation between the contents of HGF and MVD in myocardium was analyzed.


RESULTS
IHC results showed that CD34 expressions, shown as brown granules, were located on the membrane and endochylema of vascular endothelial cells. The MVD in HGF + US/MB group [ (266.9 +/- 39.8) /HPF] were highest among all the groups. The contents of HGF in myocardium were highest in HGF + US/MB group [(5.54 +/- 0.81) ng/g], and the contents of HGF in anterior wall were significantly higher than those in posterior wall (P < 0.05); the difference was also significant when compared with others groups (P < 0.01). The correlation analysis showed the contents of HGF was positively correlated with MVD in myocardium.


CONCLUSIONS
Ultrasound-targeted microbubble destruction can effectively deliver HGF into the infracted myocardium and facilitate angiogenesis, which provides a novel way in the gene therapy of myocardial infarction.
Wang
Zhi-Gang
ZG
Institute of Ultrasound Imaging, Chongqing University of Medical Sciences, Chongqing 400010, China. wzg62942443@163.com
Li
Xing-Sheng
XS
Li
Xue-Lin
XL
Yuan
Qiao-Ying
QY
Ren
Jian-Li
JL
Ran
Hai-Tao
HT
Li
Pan
P
Yang
Chun-Jiang
CJ
D000818:Animals; D016503:Drug Delivery Systems; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D045423:Microbubbles; D055806:Microvessels / Q000187:drug effects / Q000503:physiopathology; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014465:Ultrasonics; D014463:Ultrasonography
D017228:Hepatocyte Growth Factor