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The role of ADAMTS13 in acute myocardial infarction: cause or consequence?
Elise S Eerenberg1, Paul F A Teunissen2, Bert-Jan van den Born1
1Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Insights
In ST-elevation myocardial infarction (STEMI), elevated VWF and decreased ADAMTS13 were linked to intramyocardial hemorrhage but not infarct size. Recombinant ADAMTS13 did not improve outcomes in a porcine model.
Area of Science:
- Cardiology
- Hematology
- Biochemistry
Background:
- ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) cleaves von Willebrand factor (VWF).
- Elevated VWF and decreased ADAMTS13 are observed in ST-elevation myocardial infarction (STEMI) patients.
- The role of ADAMTS13 in STEMI complications like no reflow, infarct size, and intramyocardial hemorrhage (IMH) is unclear.
Purpose of the Study:
- To determine the role of ADAMTS13 in STEMI patients.
- To investigate the therapeutic potential of recombinant ADAMTS13 (rADAMTS13) in a porcine model of myocardial ischemia-reperfusion injury.
Main Methods:
- Studied 49 STEMI patients undergoing percutaneous coronary intervention (PCI), assessing VWF and ADAMTS13 levels and cardiac magnetic resonance for infarct size and IMH.
- Used a porcine model with circumflex coronary artery occlusion, administering rADAMTS13 or vehicle post-reperfusion.
- Assessed myocardial injury, infarct characteristics, and microthrombi formation via cardiac enzymes, ECG, and histopathology.
Main Results:
- STEMI patients with IMH showed significantly higher VWF activity and lower ADAMTS13 activity post-PCI compared to those without IMH.
- VWF and ADAMTS13 levels were not correlated with infarct size in STEMI patients.
- In the porcine model, rADAMTS13 administration did not alter infarct size, IMH, or microthrombi formation compared to controls.
Conclusions:
- While VWF/ADAMTS13 imbalance is associated with IMH in STEMI, it does not correlate with infarct size.
- Recombinant ADAMTS13 therapy showed no benefit in reducing infarct size or IMH in a preclinical model.
- These findings challenge the hypothesis that VWF/ADAMTS13 imbalance is a primary driver of no reflow in STEMI.
Aims:
ADAMTS13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, is a metalloprotease that cleaves von Willebrand factor (VWF). There is considerable evidence that VWF levels increase and ADAMTS13 levels decrease in ST-elevation myocardial infarction (STEMI) patients. It is unclear whether this contributes to no reflow, infarct size, and intramyocardial haemorrhage (IMH). We aimed to determine the role of ADAMTS13 in STEMI patients and to investigate the benefits of recombinant ADAMTS13 (rADAMTS13) in a porcine model of myocardial ischaemia-reperfusion.
Methods And Results:
In 49 consecutive percutaneous coronary intervention (PCI)-treated STEMI patients, blood samples were collected directly after through 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 min. rADAMTS13 or vehicle was administered intracoronary following reperfusion. Myocardial injury and infarct characteristics were assessed using cardiac enzymes, ECG, and histopathology. 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 with patients without IMH. VWF activity and ADAMTS13 activity were not related to infarct size. In rADAMTS13-treated animals, no differences in infarct size, IMH, or formation of microthrombi were witnessed compared with controls.
Conclusions:
No correlation was found between VWF/ADAMTS13 and infarct size in patients. However, patients suffering from IMH had significantly higher VWF activity and lower ADAMTS13 activity. Intracoronary administration of rADAMTS13 did not decrease infarct size or IMH in a porcine model of myocardial ischaemia-reperfusion. These data dispute the imbalance in ADAMTS13 and VWF as the cause of no reflow.
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