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
ROLE OF MATRIX METALLOPROTEINASE-2 IN THE CARDIOPROTECTIVE EFFECT OF ISCHEMIC POSTCONDITIONING. [JOURNAL ARTICLE]
Exp Physiol 2009 Oct 30.
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.
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