| ADAMTS13 deficiency exacerbates VWF-dependent acute myocardial ischemia/reperfusion injury in mice. | |
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MedLine Citation:
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PMID: 22983446 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Epidemiologic studies suggest that elevated VWF levels and reduced ADAMTS13 activity in the plasma are risk factors for myocardial infarction. However, it remains unknown whether the ADAMTS13-VWF axis plays a causal role in the pathophysiology of myocardial infarction. In the present study, we tested the hypothesis that ADAMTS13 reduces VWF-mediated acute myocardial ischemia/reperfusion (I/R) injury in mice. Infarct size, neutrophil infiltration, and myocyte apoptosis in the left ventricular area were quantified after 30 minutes of ischemia and 23.5 hours of reperfusion injury. Adamts13(-/-) mice exhibited significantly larger infarcts concordant with increased neutrophil infiltration and myocyte apoptosis compared with wild-type (WT) mice. In contrast, Vwf(-/-) mice exhibited significantly reduced infarct size, neutrophil infiltration, and myocyte apoptosis compared with WT mice, suggesting a detrimental role for VWF in myocardial I/R injury. Treating WT or Adamts13(-/-) mice with neutralizing Abs to VWF significantly reduced infarct size compared with control Ig-treated mice. Finally, myocardial I/R injury in Adamts13(-/-)/Vwf(-/-) mice was similar to that in Vwf(-/-) mice, suggesting that the exacerbated myocardial I/R injury observed in the setting of ADAMTS13 deficiency is VWF dependent. These findings reveal that ADAMTS13 and VWF are causally involved in myocardial I/R injury. |
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Authors:
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Chintan Gandhi; David G Motto; Melissa Jensen; Steven R Lentz; Anil K Chauhan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-09-14 |
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: 5224-30 Citation Subset: AIM; IM |
Affiliation:
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Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Neutralizing / pharmacology Apoptosis / drug effects, genetics, physiology Cardiotonic Agents / pharmacology Disease Progression Male Metalloendopeptidases / deficiency*, genetics, physiology* Mice Mice, Inbred C57BL Mice, Knockout Myocardial Infarction / complications, genetics, pathology Myocardial Reperfusion Injury / genetics*, pathology Myocytes, Cardiac / drug effects, metabolism, pathology, physiology Neutrophil Infiltration / genetics von Willebrand Factor / antagonists & inhibitors, genetics, immunology, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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HL062984/HL/NHLBI NIH HHS; HL063943/HL/NHLBI NIH HHS; HL076539/HL/NHLBI NIH HHS; NS024621/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Neutralizing; 0/Cardiotonic Agents; 0/von Willebrand Factor; 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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