期刊
GENE THERAPY
卷 19, 期 8, 页码 836-843出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/gt.2011.128
关键词
angiogenesis; hepatocyte growth factor; ischemic heart disease; molecular imaging; rats
类别
资金
- Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japanese Government [18390326, 22390239]
- Grants-in-Aid for Scientific Research [22390239, 24659140, 18390326] Funding Source: KAKEN
We investigated the long-term effects of human hepatocyte growth factor (HGF) gene therapy in a rat myocardial infarct model. Treatment adenovirus coexpressing the HGF therapeutic gene and the human sodium/iodide symporter (NIS) reporter gene or control adenovirus expressing the NIS gene alone were injected directly into the infarct border zone immediately after permanent coronary ligation in rats (n = 6 each). A uniform disease state was confirmed in the acute phase in terms of impaired left ventricular (LV) function by cine magnetic resonance imaging (MRI), large infarct extent by Tc-99m-tetrofosmin single-photon emission computed tomography (SPECT) and successful gene transfer and expression by (TcO4-)-Tc-99m SPECT. After a 10-week follow-up, repeated cine MRI demonstrated no significant difference in the LV ejection fraction between the time points or groups, but a significantly increased end-diastolic volume from the acute to the chronic phase without a significant difference between the groups. Capillary density was significantly higher in the treatment group, whereas arteriole density remained unchanged. Two-photon excitation fluorescence microscopy revealed extremely thin capillaries (2-5 mu m), and their irregular networks increased in the infarct border zone of the treated myocardium. Our results indicated that single HGF gene therapy alone induced an immature and irregular microvasculature.
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