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

Biomaterial-based delivery systems of nucleic acid for regenerative research and regenerative therapy

“…We have confirmed that the profile of the hydrogel degradation and release of nucleic acid is not influenced by the shape and size of hydrogel [99]. So far, the controlled release system of nucleic acids with the cationized gelatin hydrogels has succeeded in the regeneration therapies for fibrosis [73], [100], [101], [102], [103], aortic aneurysms [104], and autoimmune alopecia [105].…”

KMUP‐3 attenuates ventricular remodelling after myocardial infarction through eNOS enhancement and restoration of MMP‐9/TIMP‐1 balance

“…Infarct size was determined by 2,3-,5-triphenyltetrazolium chloride (TTC) staining, and was expressed as ratio of the surface area of the infarct wall to the entire surface area of the LV (Vandegriff et al, 2008). The heart section was also stained with Masson's trichrome to assess fibrosis as previously described (Lin et al, 2009;Yeh et al, 2010). The infarct area was visible as white and non-infarct as red after being stained with TTC.…”

Micro- and nanoparticles for treating cardiovascular disease

“…Another potential target for finely tuned delivery post-MI is MMPs. Lin et al delivered MMP-1 plasmid DNA in microparticles to reduced scarring post-MI 28 . However, MMPs have another important role in contributing to post-MI damage that was not targeted in the Lin et al study, namely breakdown of native extracellular matrix (ECM) proteins immediately following ischemic injury and cardiomyocyte death 92 .…”