title: The role of ADAMTS13 in acute myocardial infarction: cause or consequence?
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Elise S
authors.initials: ES
authors.lastname: Eerenberg
authors.affiliation: Department of Cardiology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands ICaR-VU, Amsterdam, The Netherlands.
authors.forename: Paul F A
authors.initials: PF
authors.lastname: Teunissen
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Bert-Jan
authors.initials: BJ
authors.lastname: van den Born
authors.affiliation: Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands Department of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands.
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.affiliation: Department of Cardiology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands ICaR-VU, Amsterdam, The Netherlands.
authors.forename: Maurits R
authors.initials: MR
authors.lastname: Hollander
authors.affiliation: Department of Cardiology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands ICaR-VU, Amsterdam, The Netherlands.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Jansen
authors.affiliation: Department of Cardiology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands ICaR-VU, Amsterdam, The Netherlands.
authors.forename: Ruben
authors.initials: R
authors.lastname: Tijssen
authors.affiliation: Department of Pathology and Cardiac Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jeroen A M
authors.initials: JA
authors.lastname: Beliën
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Peter M
authors.initials: PM
authors.lastname: van de Ven
authors.affiliation: Department of Cardiology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors.forename: Mohamed F
authors.initials: MF
authors.lastname: Aly
authors.affiliation: Department of Cardiology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands ICaR-VU, Amsterdam, The Netherlands.
authors.forename: Otto
authors.initials: O
authors.lastname: Kamp
authors.affiliation: ICaR-VU, Amsterdam, The Netherlands Department of Pathology and Cardiac Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Hans W
authors.initials: HW
authors.lastname: Niessen
authors.affiliation: Department of Vascular Medicine, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Pieter Willem
authors.initials: PW
authors.lastname: Kamphuisen
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Levi
authors.affiliation: Department of Cardiology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands ICaR-VU, Amsterdam, The Netherlands n.vanroyen@vumc.nl.
authors.forename: Niels
authors.initials: N
authors.lastname: van Royen
mesh_terms: D000071120:ADAMTS13 Protein / Q000008:administration & dosage* / Q000097:blood*; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007269:Injections, Intra-Arterial; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology*; D062645:Percutaneous Coronary Intervention; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage; D000072657:ST Elevation Myocardial Infarction / Q000097:blood / Q000201:enzymology* / Q000503:physiopathology / Q000628:therapy; D034421:Sus scrofa; D013997:Time Factors; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D011994:Recombinant Proteins; D014841:von Willebrand Factor; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: ADAMTS13; Acute myocardial infarction; Ischemia-reperfusion injury; No reflow; von Willebrand factor