Document Detail


ADAMTS13 deficiency exacerbates VWF-dependent acute myocardial ischemia/reperfusion injury in mice.
MedLine Citation:
PMID:  22983446     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Chintan Gandhi; David G Motto; Melissa Jensen; Steven R Lentz; Anil K Chauhan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-09-14
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:  5224-30     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
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:
HL062984/HL/NHLBI NIH HHS; HL063943/HL/NHLBI NIH HHS; HL076539/HL/NHLBI NIH HHS; NS024621/NS/NINDS NIH HHS; P01 HL062984/HL/NHLBI NIH HHS; R01 HL063943/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
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:
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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