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.
Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. xuelin@kuhp.kyoto-u.ac.jp
Xue
X
Lin
Hikari
H
Jo
Takahiro M
TM
Ishii
Masatoshi
M
Fujita
Michael
M
Fu
Keiichi
K
Tambara
Masaya
M
Yamamoto
Yasuhiko
Y
Tabata
Masashi
M
Komeda
Satoshi
S
Matsuoka
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