Grant: Travel Awards - Institute Community Support

During a heart attack (ischemia) the proteins responsible for heart beating (contractile proteins) are destroyed and this leads to irregular beating (contractile dysfunction). We have found that degradation of contractile proteins is performed by a degradation protein called matrix metalloproteinase-2 (MMP-2). Our hypothesis is that MMP-2 has different activity degrading contractile proteins depending on how serious the heart attack is. We have a system that allows us to make the rat heart work and pump as if it were inside of the body - isolated perfused heart. Using this system we simulated a heart attack by tying one of the arteries of the heart for 45 or 90 min (ischemia) followed by untying of the artery (reperfusion). This way only a region of the heart suffers ischemia while the remaining is normal. After this experiment we collected heart muscle to analyze activity of MMP-2 and contractile proteins. After 90 min of ischemia and 60 min of reperfusion heart function (pumping) was much worse than in perfused rat hearts subjected to 45 min of ischemia or no ischemia. MMP-2 activity in heart muscle shows that the longer the ischemia the more activity we detect. Also, the more activity the higher the degradation of contractile proteins, namely myosin light chain 1 (MLC1). Interestingly, MLC1 appears to only be degraded after reperfusion, not after ischemia without reperfusion. A new finding of our study was that in normal hearts (no ischemia/reperfusion) the degradation enzyme MMP-2 has different protein and activity levels in different heart regions. This study shows a novel discovery: MMP-2 has different levels and activities in different heart regions. Also, we show that heart contractile is due, in part, to increased activity of MMP-2 and degradation of MLC1 during reperfusion, not ischemia. Our results are important to understand injury to the heart during heart attacks and help develop new treatments to protect and repair the heart from ischemia.