Transgenic swine: Expression of human CD39 protects against myocardial injury

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

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)958-961
Number of pages4
JournalJournal of Molecular and Cellular Cardiology
Volume52
Issue number5
DOIs
StatePublished - May 2012

Keywords

  • CD39
  • Ectonucleoside triphosphate diphosphohydrolase 1
  • Myocardial ischemia
  • Reperfusion
  • Transgenic pig

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Transgenic swine: Expression of human CD39 protects against myocardial injury'. Together they form a unique fingerprint.

Cite this