Preconditioning decreases ischemia/reperfusion-induced release and activation of matrix metalloproteinase-2.
Release and activation of matrix metalloproteinases (MMPs) significantly contribute to myocardial stunning injury immediately after ischemia and reperfusion, however, their role in preconditioning remains unknown. We therefore examined the effects of preconditioning and subsequent ischemia/reperfusion on MMP activity in isolated rat hearts. Hearts were subjected to a preconditioning protocol (three consecutive 5-min periods of global ischemia interspersed with 5 min of reperfusion) followed by 30 min ischemia and 5 min reperfusion. To measure MMP release, coronary effluent was collected: (a) during aerobic perfusion, (b) in reperfusion following each preconditioning ischemia, and (c) during the final reperfusion following test ischemia. MMP-2 activities could be detected by gelatin zymography in the ventricles and coronary effluent samples from the perfused hearts. The levels of MMP-2 activity in the effluent were markedly increased in effluent following test ischemia from control hearts without preconditioning. This was accompanied by a decrease in corresponding tissue MMP activities. Preconditioning significantly decreased the MMP-2 activity in the coronary effluent following test ischemia/reperfusion and preserved the MMP-2 protein content and activity in the myocardium. Our results demonstrate that classic preconditioning inhibits ischemia/reperfusion induced release and activation of MMP-2. These results suggest that preconditioning may exert part of its cardioprotective effects through the reduction of MMP-2 release.
Cardiovascular Research Group, Department of Pharmacology, University of Alberta, Edmonton, AB, Canada T6G 2S2.
Manoj M
MM
Lalu
Csaba
C
Csonka
Zoltán
Z
Giricz
Tamás
T
Csont
Richard
R
Schulz
Péter
P
Ferdinandy
D000818:Animals; D015153:Blotting, Western; D004789:Enzyme Activation; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury; D013997:Time Factors
D020778:Matrix Metalloproteinase 2