Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury
Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury
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DOI：
10.1152/ajpheart.00883.2012
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发表时间：
2013-04-01
影响因子：
4.8
通讯作者：
McCully, James D.
中科院分区：
文献类型：
--
作者：
Masuzawa, Akihiro;Black, Kendra M.;McCully, James D.
Masuzawa A，Black KM，Pacak CA，Ericsson M，巴内特RJ，Drumm C，Seth P，Bloch DB，Levitsky S，科万DB，McCully JD.自体来源的线粒体移植保护心脏免受缺血再灌注损伤。Am J Physiol Endocrinol Metab 304：H966-H982，2013.首次发表于2013年1月25日; doi：10.1152/ajpheart.00883.2012.-线粒体损伤和功能障碍发生在缺血期间，并在再灌注期间显著调节心脏功能和细胞存活。我们假设在再灌注前立即移植自体来源的线粒体会改善这些影响。新西兰白色兔进行局部缺血（RI），通过暂时勒住左前降支动脉30分钟来实现。RI 29分钟后，将自体来源的线粒体（RI-线粒体; 9.7 +/- 1.7 x 10（6）/ml）或单独的载体（RI-载体）直接注射到RI区，并使心脏恢复4周。线粒体移植组RI区肌酸激酶同工酶MB、心肌肌钙蛋白I和细胞凋亡明显减少（P < 0.05）。与RI-载体（34.2 +/-3.3%，P < 0.05）相比，RI-线粒体（7.9 +/-2.9%，P < 0.05）恢复4周后的脑体积显著减小。系列超声心动图显示，RI-线粒体心脏恢复正常收缩后10分钟内再灌注开始，然而，RI-车辆心脏表现出持续的运动功能减退，在RI区在4周的恢复。心电图和光学标测研究表明，没有心律失常与自体来源的线粒体移植。体内和体外研究表明，移植的线粒体在间质空间中是明显的，并在移植后2-8小时被心肌细胞内化。移植的线粒体增强了氧消耗、高能磷酸盐合成以及细胞因子介质和蛋白质组学途径的诱导，这些介质和蛋白质组学途径在保护心肌能量学、细胞活力和增强梗死后心脏功能中是重要的。自体线粒体移植提供了一种保护心脏免受缺血再灌注损伤的新技术。
Masuzawa A, Black KM, Pacak CA, Ericsson M, Barnett RJ, Drumm C, Seth P, Bloch DB, Levitsky S, Cowan DB, McCully JD. Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury. Am J Physiol Endocrinol Metab 304: H966-H982, 2013. First published January 25, 2013; doi:10.1152/ajpheart.00883.2012.-Mitochondrial damage and dysfunction occur during ischemia and modulate cardiac function and cell survival significantly during reperfusion. We hypothesized that transplantation of autologously derived mitochondria immediately prior to reperfusion would ameliorate these effects. New Zealand White rabbits were used for regional ischemia (RI), which was achieved by temporarily snaring the left anterior descending artery for 30 min. Following 29 min of RI, autologously derived mitochondria (RI-mitochondria; 9.7 +/- 1.7 x 10(6)/ml) or vehicle alone (RI-vehicle) were injected directly into the RI zone, and the hearts were allowed to recover for 4 wk. Mitochondrial transplantation decreased (P < 0.05) creatine kinase MB, cardiac troponin-I, and apoptosis significantly in the RI zone. Infarct size following 4 wk of recovery was decreased significantly in RI-mitochondria (7.9 +/- 2.9%) compared with RI-vehicle (34.2 +/- 3.3%, P < 0.05). Serial echocardiograms showed that RI-mitochondria hearts returned to normal contraction within 10 min after reperfusion was started; however, RI-vehicle hearts showed persistent hypokinesia in the RI zone at 4 wk of recovery. Electrocardiogram and optical mapping studies showed that no arrhythmia was associated with autologously derived mitochondrial transplantation. In vivo and in vitro studies show that the transplanted mitochondria are evident in the interstitial spaces and are internalized by cardiomyocytes 2-8 h after transplantation. The transplanted mitochondria enhanced oxygen consumption, high-energy phosphate synthesis, and the induction of cytokine mediators and proteomic pathways that are important in preserving myocardial energetics, cell viability, and enhanced post-infarct cardiac function. Transplantation of autologously derived mitochondria provides a novel technique to protect the heart from ischemia-reperfusion injury.