Document Detail


Protective anti-inflammatory effect of ADAMTS13 on myocardial ischemia/reperfusion injury in mice.
MedLine Citation:
PMID:  22915644     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Coronary heart disease is a major cause of death in the western world. Although essential for successful recovery, reperfusion of ischemic myocardium is inevitably associated with reperfusion injury. To investigate a potential protective role of ADAMTS13, a protease cleaving von Willebrand factor multimers, during myocardial ischemia/reperfusion, we used a mouse model of acute myocardial infarction. We found that Adamts13(-/-) mice developed larger myocardial infarctions than wild-type control mice, whereas treatment of wild-type mice with recombinant human ADAMTS13 (rhADAMTS13) led to smaller infarctions. The protective effect of ADAMTS13 was further confirmed by a significant reduction of cardiac troponin-I release and less myocardial apoptosis in mice that received rhADAMTS13 compared with controls. Platelets adherent to the blood vessel wall were observed in few areas in the heart samples from mice treated with vehicle and were not detected in samples from mice treated with rhADAMTS13. However, we observed a 9-fold reduction in number of neutrophils infiltrating ischemic myocardium in mice that were treated with rhADAMTS13, suggesting a potent anti-inflammatory effect of ADAMTS13 during heart injury. Our data show that ADAMTS13 reduces myocardial ischemia/reperfusion injury in mice and indicate that rhADAMTS13 could be of therapeutic value to limit myocardial ischemia/reperfusion injury.
Authors:
Simon F De Meyer; Alexander S Savchenko; Michael S Haas; Daphne Schatzberg; Michael C Carroll; Alexandra Schiviz; Barbara Dietrich; Hanspeter Rottensteiner; Friedrich Scheiflinger; Denisa D Wagner
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-08-22
Journal Detail:
Title:  Blood     Volume:  120     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-21     Completed Date:  2013-02-15     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5217-23     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
ADAM Proteins / adverse effects,  pharmacokinetics,  pharmacology*,  therapeutic use
Animals
Anti-Inflammatory Agents / adverse effects,  pharmacokinetics,  pharmacology*
CHO Cells
Cardiotonic Agents / adverse effects,  pharmacokinetics,  pharmacology*
Cricetinae
Cricetulus
Cytoprotection / drug effects*,  genetics
Humans
Male
Metalloendopeptidases / genetics,  metabolism,  physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocardial Reperfusion Injury / drug therapy,  genetics,  metabolism,  prevention & control*
Recombinant Proteins / adverse effects,  pharmacokinetics,  pharmacology,  therapeutic use
Grant Support
ID/Acronym/Agency:
R01 HL041002/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Cardiotonic Agents; 0/Recombinant Proteins; EC 3.4.24.-/ADAM Proteins; EC 3.4.24.-/ADAMTS13 protein, human; EC 3.4.24.-/ADAMTS13 protein, mouse; EC 3.4.24.-/Metalloendopeptidases
Comments/Corrections
Comment In:
Blood. 2012 Dec 20;120(26):5096-7   [PMID:  23258899 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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