Impact of cardiac-specific expression of CD39 on myocardial infarct size in mice.
Impact of cardiac-specific expression of CD39 on myocardial infarct size in mice.
复制标题
CD39 心脏特异性表达对小鼠心肌梗死面积的影响。
DOI：
10.1016/j.lfs.2016.10.016
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发表时间：
2017
期刊：
影响因子：
6.1
通讯作者：
Gumina,RichardJ
中科院分区：
文献类型：
--
作者：
Smith,StephenB;Xu,Zhaobin;Novitskaya,Tatiana;Zhang,Bo;Chepurko,Elena;Pu,Xin-An;Wheeler,DebraG;Ziolo,Mark;Gumina,RichardJ
Aims 先前的工作表明，缺血预处理会增加心脏中 CD39 的水平，有助于心脏保护。因此，我们检查了 CD39 的靶向心脏表达是否可以预防心肌损伤。 主要方法 产生、鉴定具有心脏特异性表达人 CD39 (αMHC/hCD39-Tg) 的小鼠，对其进行表征，并对其进行左冠状动脉缺血再灌注损伤，并对损伤后 24 小时的梗死面积进行量化。 主要发现与 WT 同窝小鼠相比，αMHC/hCD39-Tg 小鼠的心脏 ATP 酶和 ADP 酶活性有所增加。 αMHC/hCD39-小鼠中增加的活性被 CD39 拮抗剂多氧钨酸钠 (POM-1) 抑制。通过超声心动图测量基础心脏功能显示，αMHC/hCD39-Tg 小鼠的静息心率较低，每搏输出量增加。与 WT 小鼠相比，αMHC/hCD39-Tg 小鼠在应对心肌缺血时更好地保留了收缩和舒张功能。 Tau 的比较还揭示了 αMHC/hCD39-Tg 心脏缺血期间保留的心脏舒张。对 60 分钟缺血和 24 小时再灌注反应的心肌梗塞面积的评估表明，αMHC/hCD39-Tg 心脏的梗塞面积显着减小。对分离心肌细胞的分析显示，WT 和 αMHC/hCD39-Tg 心肌细胞之间的钙瞬变没有基础差异。然而，响应异丙肾上腺素刺激，αMHC/hCD39 心肌细胞中的钙瞬变呈降低趋势，表明响应代谢应激的钙积累较少。意义 CD39 的心脏特异性表达可减少缺血再灌注损伤后的心肌功能障碍和梗塞面积。增加心脏中的核苷酸酶表达可能是保护心脏免受缺血性损伤的新方法。
AimsPrior work suggests that ischemic preconditioning increases the level of CD39 in the heart and contributes to cardiac protection. Therefore, we examined if targeted cardiac expression of CD39 protects against myocardial injury.Main methodsMice with cardiac-specific expression of human CD39 (αMHC/hCD39-Tg) were generated, characterized and subjected to left coronary artery ischemia-reperfusion injury and infarct size at 24 h following injury quantified.Key findingsαMHC/hCD39-Tg mice have increased in cardiac ATPase and ADPase activity compared to WT littermates. The increased activity in αMHC/hCD39-mice was inhibited by the CD39 antagonist sodium polyoxotungstate (POM-1). Measurement of basal cardiac function by echocardiography revealed that αMHC/hCD39-Tg mice have a lower resting heart rate and increased stroke volume. In response to myocardial ischemia, systolic and diastolic function was better preserved in αMHC/hCD39-Tg compared to WT mice. Comparison of Tau also revealed preserved cardiac relaxation during ischemia in αMHC/hCD39-Tg hearts. Assessment of myocardial infarct size in response to 60 min of ischemia and 24 h of reperfusion demonstrated a significant reduction in infarct size in αMHC/hCD39-Tg hearts. Analysis of isolated cardiomyocytes revealed no basal difference in calcium transients between WT and αMHC/hCD39-Tg cardiomyocytes. However, in response to isoproterenol stimulation, there was a trend toward lower calcium transients in αMHC/hCD39 cardiomyocytes suggesting less calcium accumulation in response to metabolic stress.SignificanceCardiac-specific expression of CD39 reduces myocardial dysfunction and infarct size following ischemia-reperfusion injury. Increasing nucleotidase expression in the heart may be a novel approach to protect the heart from ischemic injury.