Controlled release of matrix metalloproteinase-1 plasmid DNA prevents left ventricular remodeling in chronic myocardial infarction of rats

Xue Lin, Hikari Jo, Takahiro M. Ishii, Masatoshi Fujita, Michael Fu, Keiichi Tambara, Masaya Yamamoto, Yasuhiko Tabata, Masashi Komeda, Satoshi Matsuoka

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2315-2321
Number of pages7
JournalCirculation Journal
Volume73
Issue number12
DOIs
Publication statusPublished - 2009

Keywords

  • Current (INCX) of Na/Ca exchange (NCX)
  • Matrix metalloproteinase-1
  • Microspheres
  • Myocardial infarction
  • Single cardiomyocyte shortening

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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