期刊
CIRCULATION JOURNAL
卷 73, 期 12, 页码 2315-2321出版社
JAPANESE CIRCULATION SOC
DOI: 10.1253/circj.CJ-09-0379
关键词
Current (I-NCX) of Na/Ca exchange (NCX); Matrix metalloproteinase-1; Microspheres; Myocardial infarction; Single cardiomyocyte shortening
资金
- Ministry of Education. Culture, Sports, Science and Technology Japan [13470271, 17590186]
- Grant-in-Aid for Scientific Research (KAKENHI), Kyoto, Japan [19P07085]
- Japan Society for Promotion of Science (JSPS)
- Grants-in-Aid for Scientific Research [17590186, 13470271] Funding Source: KAKEN
Background: The present study investigated whether administration of controlled release matrix metalloproteinase-1 (MMP-1) plasmid DNA prevents left ventricular(LV) remodeling in a rat chronic myocardial infarction (MI) model. Methods and Results: Rats with a moderate-sized MI were randomized to 2 groups: injection of phosphate buffered saline (PBS) containing microspheres into the peri-infarct area (MI group, n=14) and injection of cationized gelatin microspheres incorporating MMP-1 plasmid DNA (MI+MMP-1 group, 50 mu g MMP-1/20 mu l; n=14). As a control group (n=14), rats received neither the coronary artery ligation nor the injection of PBS. Echocardiography, cardiac catheterization and histological studies were performed. At 2 and 4 weeks after the treatment, the MI+MMP-1 group had smaller LV end-diastolic and end-systolic dimensions, better fractional area change and smaller akinetic areas than the MI group. The LV end-systolic elastance and time constant of isovolumic relaxation were also better in the MI+MMP-1 group compared with the MI group 4 weeks after the treatment. Fibrosis evaluated with Masson's trichrome staining was less in the MI+MMP-1 group than the MI group. Conclusions: Gelatin microspheres for the controlled release of MMP-1 plasmid DNA are promising for improving cardiac remodeling and function when they are administered during the chronic phase of MI. (Circ J 2009; 73: 2315-2321)
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