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


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 microg MMP-1/20 microl; 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.
Lin
Xue
X
Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. xuelin@kuhp.kyoto-u.ac.jp
Jo
Hikari
H
Ishii
Takahiro M
TM
Fujita
Masatoshi
M
Fu
Michael
M
Tambara
Keiichi
K
Yamamoto
Masaya
M
Tabata
Yasuhiko
Y
Komeda
Masashi
M
Matsuoka
Satoshi
S
D000818:Animals; D002908:Chronic Disease; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D005355:Fibrosis; D005780:Gelatin; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000235:genetics; D008564:Membrane Potentials; D008863:Microspheres; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D010957:Plasmids; D051381:Rats; D011917:Rats, Inbred Lew; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D013997:Time Factors; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling / Q000235:genetics
D003692:Delayed-Action Preparations; D019831:Sodium-Calcium Exchanger; D005780:Gelatin; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1