| Protective anti-inflammatory effect of ADAMTS13 on myocardial ischemia/reperfusion injury in mice. | |
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MedLine Citation:
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PMID: 22915644 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-08-22 |
Journal Detail:
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Title: Blood Volume: 120 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-21 Completed Date: 2013-02-15 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 5217-23 Citation Subset: AIM; IM |
Affiliation:
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Immune Disease Institute, Boston, MA 02115, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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ADAM Proteins
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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:
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R01 HL041002/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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:
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Blood. 2012 Dec 20;120(26):5096-7
[PMID:
23258899
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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