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Circulation. 2007 Oct 16;116(16):1784-94. Epub 2007 Oct 1.

CD39/ectonucleoside triphosphate diphosphohydrolase 1 provides myocardial protection during cardiac ischemia/reperfusion injury.

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  • 1Department of Anesthesiology and Intensive Care Medicine, University Hospital, Tübingen, Germany.

Erratum in

  • Circulation. 2007 Oct 30;116(18):e514.

Abstract

BACKGROUND:

Extracellular adenosine, generated from extracellular nucleotides via ectonucleotidases, binds to specific receptors and provides cardioprotection from ischemia and reperfusion. In the present study, we studied ecto-enzymatic ATP/ADP-phosphohydrolysis by select members of the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) family during myocardial ischemia.

METHODS AND RESULTS:

As a first step, we used a murine model of myocardial ischemia and in situ preconditioning and performed pharmacological studies with polyoxometalate 1, a potent E-NTPDase inhibitor (Na6[H2W12O40]). Polyoxometalate 1 treatment increased infarct sizes and abolished beneficial effects of preconditioning. To define relative contributions of distinct E-NTPDases, we investigated transcriptional responses of E-NTPDases 1 to 3 and 8 to preconditioning. We noted robust and selective induction of E-NTPDase 1 (CD39) transcript and protein. Histological analysis of preconditioned myocardium localized CD39 induction to endothelia and myocytes. Cd39-/- mice exhibited larger infarct sizes with ischemia (cd39+/+ 43.0+/-3.3% versus cd39-/- 52%+/-1.8; P<0.05), and cardioprotection was abrogated by preconditioning (cd39+/+ 13.3%+/-1.5 versus cd39-/- 50.5%+/-2.8; P<0.01). Heightened levels of injury after myocardial ischemia and negligible preconditioning benefits in cd39-/- mice were corrected by infusion of the metabolic product (AMP) or apyrase. Moreover, apyrase treatment of wild-type mice resulted in 43+/-4.2% infarct size reduction (P<0.01).

CONCLUSIONS:

Taken together, these studies reveal E-NTPDase 1 in cardioprotection and suggest apyrase in the treatment of myocardial ischemia.

PMID:
17909107
[PubMed - indexed for MEDLINE]
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