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/MB group, and 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.
Key words
ultrasound microbubble /
depatocyte crowtd factor /
anciocenesis
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References
[1]Weidner N. Intratumor microvessel density as a prognostic factor in cancer[J]. Am J Pathol, 1995,147(1):9-19.
[2]Sasaki H, Fukuda S, Otani H,et al. Hypoxic preconditioning triggers myocardial angiogenesis: a novel approach to enhance contractile functional reserve in rat with myocardial infarction[J]. J Mol Cell Cardiol, 2002,34(3):335-348.
[3]Nakagami H, Morishita R, Yamamoto K, et al. Mitogenic and antiapoptotic actions of hepatocyte growth factor through ERK, STAT3, and AKT in endothelial cells[J]. Hypertension, 2001,37(2 Part 2):581-586.
[4]Yasuda S, Goto Y, Baba T, et al. Enhanced secretion of cardiac hepatocyte growth factor from an infarct region is associated with less severe ventricular enlargement and improved cardiac function[J]. J Am Coll Cardiol, 2000,36(1):115-121.
[5]Ahmet I, Sawa Y, Yamaguchi T, et al. Gene transfer of hepatocyte growth factor improves angiogenesis and function of chronic ischemic myocardium in canine heart[J]. Ann Thorac Surg, 2003,75(4):1283-1287.
[6]Ueda H, Nakamura T, Matsumoto K, et al. A potential cardioprotective role of hepatocyte growth factor in myocardial infarction in rats[J]. Cardiovasc Res, 2001,51(1):41-50.
[7]Nakamura T, Mizuno S, Matsumoto K, et al. Myocardial protection from ischemia/reperfusion injury by endogenous and exogenous HGF[J]. J Clin Invest, 2000,106(12):1511-1519.
[8]Taniyama Y, Morishita R, Nakagami H, et al. Potential contribution of a novel antifibrotic factor, hepatocyte growth factor, to prevention of myocardial fibrosis by angiotensin Ⅱ blockade in cardiomyopathic hamsters[J]. Circulation, 2000,102(2):246-252.
[9]Zhigang W, Zhiyu L, Haitao R, et al. Ultrasound-mediated microbubble destruction enhances VEGF gene delivery to the infarcted myocardium in rats[J]. Clin Imaging, 2004,28(6):395-398.
[10]凌智瑜, 王志刚, 冉海涛,等. 超声微泡造影剂对心肌组织毛细血管通透性的影响实验研究[J]. 中国超声医学杂志, 2004,20(5):327-330.
[11]Price RJ, Skyba DM, Kaul S, et al. Delivery of colloidal particles and red blood cells to tissue through microvessel ruptures created by targeted microbubble destruction with ultrasound[J]. Circulation, 1998,98(13):1264-1267.
[12]Skyba DM, Price RJ, Linka AZ, et al. Direct in vivo visualization of intravascular destruction of microbubbles by ultrasound and its local effects on tissue[J]. Circulation, 1998,98(4):290-293.
[13]Kaygusuz G, Tulunay O, Baltaci S, et al. Microvessel density and regulators of angiogenesis in malignant and nonmalignant prostate tissue[J]. Int Urol Nephrol, 2007,39(3):841-850.
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