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Matrix metalloproteinase-2: an emerging biomarker for reperfusion injury following percutaneous coronary intervention
  1. Xiaohu Fan,
  2. Richard Schulz
  1. Departments of Paediatrics and Pharmacology, Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada
  1. Correspondence to Dr Richard Schulz, Cardiovascular Research Centre, 4-62 HMRC, University of Alberta, Edmonton, AB T6G 2S2 Canada; richard.schulz{at}ualberta.ca

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In the past three decades, percutaneous coronary intervention has become the standard of treatment in acute coronary syndromes. However, reopening of acutely occluded coronary arteries paradoxically causes reperfusion injury characterised by a localised, acute inflammatory response and myocardial damage. Because of the lack of good plasma biomarkers, reperfusion-induced myocardial damage and its contribution to final infarct size is difficult to evaluate.

Biomarkers play an important role in diagnosis, prognosis and risk evaluation in the treatment of cardiovascular diseases. Ideal biomarkers should not only have a good sensitivity and dynamic range, but should also correlate well to the therapeutic response. There is increasing evidence that matrix metalloproteinase 2 (MMP-2) may be such a biomarker based on recent clarification of its pathophysiological significance in acute myocardial infarction.

Matrix metalloproteinases (MMP) are a family of zinc-dependent endopeptidases that are synthesised as zymogens. Of particular interest with regard to the heart are the gelatinases MMP-2 and MMP-9, as the former is found in cardiac myocytes,1 cardiac fibroblasts2 and endocardial cells,3 whereas the latter is found in activated neutrophils within infarct tissue. MMP activities are regulated by a family of endogenous protease inhibitors, the tissue inhibitors of metalloproteinases (TIMP-1–4). MMP were initially recognised for their ability to effect tissue remodelling by proteolysis of several proteins which make up the extracellular matrix. Such remodelling processes take course over periods of weeks to months. More recently, however, a number of studies have demonstrated that MMP-2 plays a key role in acute processes in heart muscle with a timescale of seconds to hours during reperfusion following experimental ischaemia in the heart.

We have shown that MMP-2 is directly involved in acute myocardial stunning injury seen …

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