The role of ADAMTS13 in acute myocardial infarction:Cause or consequence?

Abstract

BACKGROUND ADAMTS13 is a metalloprotease that cleaves von Willebrand factor (VWF), thereby reducing its prothrombotic properties. There is considerable evidence that VWF levels increase and ADAMTS13 levels decrease in STEMI patients. It is unclear if this contributes to no reflow, infarct size and intramyocardial hemorrhage (IMH). The aim of this study was to determine the role of ADAMTS13 in patients with acute myocardial infarction; and to investigate the benefits of recombinant (r)ADAMTS13 in a porcine model of myocardial ischemia-reperfusion with dual antiplatelet therapy and heparin. METHODS In 49 consecutive PCI-treated STEMI patients, blood samples were collected directly after and up to 7 days following PCI. Cardiac magnetic resonance was performed 4-6 days after PCI to determine infarct size and IMH. In 23 Yorkshire swine, the circumflex coronary artery was occluded for 75 minutes by a balloon catheter. rADAMTS13 or vehicle was administered intracoronary following reperfusion. Myocardial injury and infarct characteristics were assessed using cardiac enzymes, ECG, and histopathology. RESULTS In patients with IMH, VWF activity and VWF antigen were significantly elevated directly after PCI and for all subsequent measurements, and ADAMTS13 activity significantly decreased at 4 and 7 days following PCI; in comparison to patients without IMH. VWF activity and ADAMTS13 activity were not related to infarct size. For rADAMTS13 treated animals no differences in myocardial infarct size, IMH, or formation of microthrombi were witnessed in comparison to controls. CONCLUSIONS No correlation was witnessed between VWF/ ADAMTS13 and infarct size in patients; and intracoronary administration of rADAMTS13 did not decrease infarct size or IMH in a porcine model of myocardial ischemia-reperfusion. These data dispute the imbalance in ADAMTS13 and VWF as the cause of no reflow. Restoring the imbalance between ADAMTS13 and VWF most likely will not be beneficial in STEMI patients already treated with standard antiplatelet and anticoagulant therapy. (Figure Presented)