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 R

EXPERIMENTAL PHYSIOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

Año: 2010 vol. 95 p. 274 - 281

0958-0670

The activation of matrix metalloproteinases (MMPs) contributes to myocardial injury at theonset of reperfusion; however, their role in ischaemic postconditioning is unknown. Theaim of the present study was to examine the effects of ischaemic postconditioning on MMPactivity in isolated rabbit hearts. The isolated rabbit hearts were subjected to 30min of globalischaemia followed by 180 min of reperfusion (I/R group; n =8). In the Postcon group (n =8),a postconditioning protocol was performed (2 cycles of 30 s reperfusion–ischaemia). In otherexperiments, we added doxycycline, an MMP inhibitor, at 25 (n =7) or 50 μmol l−1 (n =8)during the first 2 min of reperfusion. Coronary effluent and left ventricular tissue were collectedduring pre-ischaemic conditions and at different times during the reperfusion period tomeasureMMP-2 activity and cardiac protein nitrotyrosinylation.We evaluated ventricular function andinfarct size. In the I/R group, infarct size was 32.1±5.2%; Postcon reduced infarct size to9.5±3.8% (P <0.05) and inhibited MMP-2 activity during reperfusion. The administrationof doxycycline at 50 μmol l−1 inhibited MMP-2 activity and cardiac protein nitrotyrosinylationand reduced the infarct size to 9.7±2.8% (P <0.05). A lower dose of doxycycline (25 μmol l−1)failed to inhibit MMP-2 activity and did not modify the infarct size. Our results stronglysuggest that ischaemic postconditioning may exert part of its cardioprotective effects throughthe inhibition of MMP-2 activity.