[Therapeutic angiogenesis induced by hepatocyte growth factor directed by ultrasound-targeted microbubble destruction].

Abstract

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.

CONCLUSION:

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.

• Authors: Zhi-Gang Wang, Xing-Sheng Li, Xue-Lin Li, Qiao-Ying Yuan, Jian-Li Ren, Hai-Tao Ran, Pan Li, Chun-Jiang Yang
• Journal: Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae (Zhongguo Yi Xue Ke Xue Yuan Xue Bao) Vol. 30 Issue 1 Pg. 5-9 (Feb 2008) ISSN: 1000-503X [Print] China
• PMID: 18361044 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hepatocyte Growth Factor

Topics

• Animals
• Drug Delivery Systems
• Hepatocyte Growth Factor (administration & dosage, therapeutic use)
• Microbubbles
• Microvessels (drug effects, physiopathology)
• Myocardial Infarction (diagnostic imaging, drug therapy, physiopathology)
• Neovascularization, Physiologic (drug effects)
• Rats
• Rats, Wistar
• Ultrasonics
• Ultrasonography