CD39/ectonucleoside triphosphate diphosphohydrolase 1 provides myocardial protection during cardiac ischemia/reperfusion injury
CD39/ectonucleoside triphosphate diphosphohydrolase 1 provides myocardial protection during cardiac ischemia/reperfusion injury
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DOI：
10.1161/circulationaha.107.690180
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发表时间：
2007-10-16
期刊：
影响因子：
37.8
通讯作者：
Eltzschig, Holger K.
中科院分区：
文献类型：
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作者：
Koehler, David;Eckle, Tobias;Eltzschig, Holger K.
细胞外腺苷，通过胞外核苷酸酶从细胞外核苷酸产生，结合特异性受体，提供心肌缺血和再灌注保护。在本研究中，我们研究了胞外酶ATP/ADP-磷酸水解的选择成员的胞外核苷三磷酸二磷酸水解酶，方法和结果-作为第一步，我们使用心肌缺血和原位预处理的小鼠模型，并使用聚氧乙烯酸1，一种有效的E-NTPD酶抑制剂（Na-6[H2 W12 O 40]）-聚氧代-金属盐I处理增加了梗死面积并消除了预处理的有益作用。为了确定不同的E-NTPDases的相对贡献，我们研究了E-NTPDases I至3和8对预处理的转录反应。我们注意到E-NTPD酶1（CD 39）转录物和蛋白质的稳健和选择性诱导。预处理心肌的组织学分析定位于内皮和肌细胞的CD 39诱导。CD 39（-/-）小鼠表现出更大的缺血梗死面积（CD 39（+/+）43.0 +/-3.3%vsCD 39（-/-）52%+/- 1.8; P
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 (Na-6[H2W12O40])- Polyoxo- metalate I 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 I 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