title: Matrix metalloproteinase-2 is activated during ischemia/reperfusion in a model of myocardial infarction.
abstract: 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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Pharmacology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Virgilio J J
authors.initials: VJ
authors.lastname: Cadete
authors.forename: Steven A
authors.initials: SA
authors.lastname: Arcand
authors.forename: Bradley M
authors.initials: BM
authors.lastname: Chaharyn
authors.forename: Adrian
authors.initials: A
authors.lastname: Doroszko
authors.forename: Jolanta
authors.initials: J
authors.lastname: Sawicka
authors.forename: Darrell D
authors.initials: DD
authors.lastname: Mousseau
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Sawicki
mesh_terms: D000818:Animals; D054059:Coronary Occlusion / Q000473:pathology; D004195:Disease Models, Animal; D057075:Enzyme Assays / Q000379:methods; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D018994:Myosin Light Chains / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D018994:Myosin Light Chains; D020778:Matrix Metalloproteinase 2