BACKGROUND: The degradation of myosin light chain 1 (MLC1) by matrix metalloproteinase-2 (MMP-2) during ischemia/reperfusion has been implicated in the development of cardiac dysfunction. Our objective was to elucidate the role of MMP-2 and MLC1 in the development of cardiac injury and dysfunction in a model of left anterior descending (LAD) coronary artery occlusion. METHODS: Adult rats (300-350 g) were anaesthetized, and the isolated hearts were retrogradely perfused in a Langendorff apparatus. The LAD was stabilized for 25 minutes and occluded for either 45 or 90 minutes and then reperfused. Cardiac function (evaluated as rate-pressure product) was significantly decreased in the reperfused hearts subjected to 90 minutes of LAD occlusion in comparison with hearts subjected to either sham or 45 minutes of occlusion. Ninety minutes of occlusion resulted in 60% of infarct. RESULTS: MMP-2 activity, measured by gelatin zymography, was significantly increased following occlusion as well as reperfusion. An increased degradation of MLC1 was observed at the end of reperfusion, but not at the end of occlusion, which most likely was because of the compensatory increase in tissue inhibitor of matrix metalloproteinases-4 (TIMP-4) during occlusion, but not reperfusion. CONCLUSION: We demonstrate that MMP-2 activation is an ischemic event that extends into the reperfusion phase, while MLC1 degradation in response to ischemia/reperfusion is strictly a reperfusion event. MLC1 degradation during occlusion is prevented by a compensatory increase in the levels of TIMP-4.
BACKGROUND: The degradation of myosin light chain 1 (MLC1) by matrix metalloproteinase-2 (MMP-2) during ischemia/reperfusion has been implicated in the development of cardiac dysfunction. Our objective was to elucidate the role of MMP-2 and MLC1 in the development of cardiac injury and dysfunction in a model of left anterior descending (LAD) coronary artery occlusion. METHODS: Adult rats (300-350 g) were anaesthetized, and the isolated hearts were retrogradely perfused in a Langendorff apparatus. The LAD was stabilized for 25 minutes and occluded for either 45 or 90 minutes and then reperfused. Cardiac function (evaluated as rate-pressure product) was significantly decreased in the reperfused hearts subjected to 90 minutes of LAD occlusion in comparison with hearts subjected to either sham or 45 minutes of occlusion. Ninety minutes of occlusion resulted in 60% of infarct. RESULTS:MMP-2 activity, measured by gelatin zymography, was significantly increased following occlusion as well as reperfusion. An increased degradation of MLC1 was observed at the end of reperfusion, but not at the end of occlusion, which most likely was because of the compensatory increase in tissue inhibitor of matrix metalloproteinases-4 (TIMP-4) during occlusion, but not reperfusion. CONCLUSION: We demonstrate that MMP-2 activation is an ischemic event that extends into the reperfusion phase, while MLC1 degradation in response to ischemia/reperfusion is strictly a reperfusion event. MLC1 degradation during occlusion is prevented by a compensatory increase in the levels of TIMP-4.
Authors: Michael A J Moser; Steve Arcand; Han-Bin Lin; Chris Wojnarowicz; Jolanta Sawicka; Tamalina Banerjee; Yigang Luo; Gavin R Beck; Patrick P Luke; Grzegorz Sawicki Journal: PLoS One Date: 2016-06-21 Impact factor: 3.240
Authors: Jakub Mochol; Jakub Gawrys; Damian Gajecki; Ewa Szahidewicz-Krupska; Helena Martynowicz; Adrian Doroszko Journal: Int J Mol Sci Date: 2021-05-12 Impact factor: 5.923