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

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)