Role of matrix metalloproteinase-2 in the cardioprotective effect of ischemic postconditioning

DONATO M; D´ANNUNZIO V; BUCHHOLZ B; MIKSZTOWICZ V; LORENZO CARRIÓN C; VALDEZ LB; ZAOBORNYJ T; SCHREIER L; WIKINSKI R; BOVERIS A; BERG G; GELPI RJ

EXPERIMENTAL PHYSIOLOGY.

Wiley-Blackwell

Año: 2010 vol. 95 p. 274 - 281

0958-0670

The activation of matrix metalloproteinases (MMPs) contributes to myocardial injury at the onset of reperfusion; however, their role in ischemic postconditioning is unknown. Aim: to examine the effects of ischemic postconditioning on MMP activity in isolated rabbit hearts.Methods: Isolated rabbit hearts were subjected to 30 min of global ischemia followed by 180 min of reperfusion (I/R group; n=8). In Postcon group (n=8), a postconditioning protocol was performed (two cycles of 30 sec reperfusion/ischemia). In other experiments we added doxycycline an MMP inhibitor, at 25 (n=7) and 50 mumol/L (n=8), respectively during the first 2 min of reperfusion. Coronary effluent and left ventricular tissue were taken during pre-ischemic conditions and at different times of the reperfusion period to measure MMP-2 activity and cardiac protein nitrotyrosinylation. We evaluated ventricular function and infarct size. Results: In the I/R group, infarct size was 32.1+/-5.2 %; Postcon reduced infarct size to 9.5+/-3.8 % (p<0.05) and inhibited MMP-2 activity during reperfusion. The administration of doxycycline at 50 mumol/L inhibited MMP-2 activity, cardiac protein nitrotyrosinylation and reduced infarct size to 9.7+/-2.8 % (p<0.05). A lower dose of doxycycline (25 mumol/L) failed to inhibit MMP-2 activity and did not modify the infarct size. Conclusion: Our results strongly suggest that ischemic postconditioning may exert part of its cardioprotective effects through the inhibition of MMP-2 activity.