Controlled Release of Matrix Metalloproteinase-1 Plasmid DNA Prevents Left Ventricular Remodeling in Chronic Myocardial Infarction of Rats

• Lin Xue

  Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University Human Health Sciences, Graduate School of Medicine, Kyoto University

• Jo Hikari

  Department of Physiology and Biophysics, Graduate School of Medicine, Kyoto University

• Ishii Takahiro M

  Department of Physiology, Neurobiology, Graduate School of Medicine, Kyoto University

• Fujita Masatoshi

  Human Health Sciences, Graduate School of Medicine, Kyoto University

• Fu Michael

  Department of Cardiovascular Research, Sahlgrenska University Hospital/Sahlgrenska, University of Göteborg

• Tambara Keiichi

  Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University

• Yamamoto Masaya

  Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University

• Tabata Yasuhiko

  Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University

• Komeda Masashi

  Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University Department of Cardiovascular Surgery, Nagoya Heart Center

• Matsuoka Satoshi

  Department of Physiology and Biophysics, Graduate School of Medicine, Kyoto University

Abstract

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 μg MMP-1/20 μl; 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)<br>

Journal

• Circulation Journal

  Circulation Journal 73 (12), 2315-2321, 2009

  The Japanese Circulation Society

Keywords

• Current (<i>I</i>_NCX) of Na/Ca exchange (NCX)
• Matrix metalloproteinase-1
• Microspheres
• Myocardial infarction
• Single cardiomyocyte shortening

Details

• CRID: 1390282680079189632
• NII Article ID: 10025938557
• NII Book ID: AA11591968
• DOI: 10.1253/circj.cj-09-0379
• ISSN: 13474820
• ISSN: 13469843
• Web Site: http://www.jstage.jst.go.jp/article/circj/73/12/73_CJ-09-0379/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2010113128
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed