Abstract 223: Control-release of MMP-1 Plasmid DNA Improved Contractility and Na/Ca Exchange of Cardiomyocytes Isolated from Rat Chronic Myocardial Infarction Heart
Background: We reported that the fibrolytic function of matrix metalloproteinase 1 (MMP-1) benefits the graft development of skeletal myoblast (SM) in rat chronic myocardial infarction (MI) heart possibly by securing enough space for myotubes to grow. To assess whether the alternation of extracellular matrix by the MMP-1 induction improves the cardiomyocyte function, we electro-physiologically studied the function of isolated cardiomyocyte.
Method: MI was induced in rats by ligating anterior-descending coronary artery. Four weeks later, 20 Lewis rats with MI were randomized into two Groups (Gps). Gp I had a saline injection to the infarct area (n=10); Gp II received MMP-1 injection (50μg/20μl; n=10). MMP-1 was given as cationized gelatin microspheres incorporating MMP-1 plasmid DNA. Gp III was normal control (n=10). Myocytes were isolated from left ventricle by perfusing collagenase. Cell shortening (%, 0.1 Hz stimulation), action potential and the Na/Ca exchange current (INCX) were measured. Expression of Na/Ca exchange (NCX) was evaluated by Northern blot from 3 rats of each group. Statistical analyses were performed using ANOVA and Student-Newman-Keul’s method.
Results: In Gp I, cell shortening (9.55±1.63 %) was attenuated and the INCX density (1.20±0.19 pA/pF) was increased when compared to Gp III (13.44±0.93 % and 0.69±0.15 pA/pF, respectively, p<0.01). MMP-1 treatment improved cell shortening (GP II, 16.04±1.01 %) to a similar level of Gp III. However, time to the peak of contraction prolonged in Gp II (136.69±9.93 ms) compared to Gp I (96.20±5.62 ms, p<0.01), while no difference in action potential duration was observed. The INCX density significantly decreased in Gps II (0.42±0.05 pA/pF) when compared to Gp I, while NCX mRNA level in Gps II was similar to Gp I, but larger than Gp III by 34%.
Conclusions: The results indicated that control-release of MMP1 improves the contractility of cardiomyocytes isolated from rat hearts with chronic myocardial infarction. This improvement was related to attenuation of NCX function. Reduction of extracellular matrix by the MMP-1 may functionally attenuate NCX without affecting the expression level.