| Transgenic swine: expression of human CD39 protects against myocardial injury. | |
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MedLine Citation:
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PMID: 22269791 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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CD39 (ectonucleoside triphosphate diphosphohydrolase-1; ENTPD-1) rapidly hydrolyzes ATP and ADP to AMP; AMP is hydrolyzed by ecto-5'-nucleotidase (CD73) to adenosine, an anti-thrombotic and cardiovascular protective mediator. While expression of human CD39 in a murine model of myocardial ischemia/reperfusion (I/R) injury confers cardiac protection, the translational therapeutic potential of these findings requires further testing in a large animal model. To determine if transgenic expression of CD39 reduces infarct size in a swine model of myocardial ischemia/reperfusion injury, transgenic pigs expressing human CD39 (hCD39) were generated via somatic cell nuclear transfer and characterized. Expression of hC39 in cardiac tissue was confirmed by immunoblot and immunohistochemistry. Myocardial I/R injury was induced by intracoronary balloon inflation in the left anterior descending (LAD) artery for 60 min followed by 3 hours of reperfusion. The ischemic area was delineated by perfusion with 5% phthalo blue and the myocardial infarct size was determined by triphenyl tetrazolium chloride (TTC) staining. During ischemia, the rate-pressure product was significantly lower in control versus hCD39-Tg swine. Following reperfusion, compared to littermate control swine, hCD39-Tg animals displayed a significant reduction in infarct size (hCD39-Tg: 17.2 ± 4.3% vs. Control: 44.7 ± 5.2%, P=0.0025). Our findings demonstrate for the first time that the findings in transgenic mouse models translate to large animal transgenic models and validate the potential to translate CD39 into the clinical arena to attenuate human myocardial ischemia/reperfusion injury. |
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Authors:
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Debra G Wheeler; Matthew E Joseph; Shouvik D Mahamud; William L Aurand; Peter J Mohler; Vincent J Pompili; Karen M Dwyer; Mark B Nottle; Sharon J Harrison; Anthony J F d'Apice; Simon C Robson; Peter J Cowan; Richard J Gumina |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-01-12 |
Journal Detail:
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Title: Journal of molecular and cellular cardiology Volume: 52 ISSN: 1095-8584 ISO Abbreviation: J. Mol. Cell. Cardiol. Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-04-16 Completed Date: 2012-08-07 Revised Date: 2013-05-03 |
Medline Journal Info:
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Nlm Unique ID: 0262322 Medline TA: J Mol Cell Cardiol Country: England |
Other Details:
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Languages: eng Pagination: 958-61 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Ltd. All rights reserved. |
Affiliation:
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Division of Cardiovascular Medicine, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210-1252, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Genetically Modified Antigens, CD / biosynthesis*, genetics Apyrase / biosynthesis*, genetics Blood Pressure Coronary Vessels / pathology Heart Rate Heart Ventricles / metabolism, pathology Humans Ischemia / metabolism, pathology Myocardial Reperfusion Injury / metabolism*, pathology Promoter Regions, Genetic Recombinant Proteins / biosynthesis, genetics Swine / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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HL 094703/HL/NHLBI NIH HHS; HL096038/HL/NHLBI NIH HHS; K08 HL094703-03/HL/NHLBI NIH HHS; P01 AI045897/AI/NIAID NIH HHS; R21 HL096038-02/HL/NHLBI NIH HHS; U01 AI066331/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/Recombinant Proteins; EC 3.6.1.5/Apyrase; EC 3.6.1.5/CD39 antigen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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