Role of Mitogen-Activated Protein Kinases in Myocardial Ischemia-Reperfusion Injury during Heart Transplantation.
Role of Mitogen-Activated Protein Kinases in Myocardial Ischemia-Reperfusion Injury during Heart Transplantation.
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DOI：
10.1155/2012/928954
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发表时间：
2012
影响因子：
2.5
通讯作者：
Moccetti T
中科院分区：
文献类型：
--
作者：
Vassalli G;Milano G;Moccetti T
在实体器官移植中，在器官获取、储存和再灌注期间的缺血/再灌注（IR）损伤对于移植物是不可避免的有害事件，因为其放大了移植物炎症和排斥。细胞内丝裂原活化蛋白激酶（MAPK）信号通路调节IR损伤期间的炎症和细胞存活。四个最佳表征的MAPK亚家族是c-Jun NH 2-末端激酶（JNK）、细胞外信号调节激酶-1/2（ERK 1/2）、p38 MAPK和大MAPK-1（BMK 1/ERK 5）。在这里，我们审查的作用，MAPK激活在心肌IR损伤，因为它发生在心脏移植。我们目前关于MAPK激活和心脏保护的知识大多来自于非移植心脏的预处理和后处理研究。JNK和p38 MAPK激活参与了长时间低温保存后心肌的IR损伤。p38 MAPK抑制可改善冷保存、复温和再灌注后的心功能。迄今为止，小分子p38 MAPK抑制剂已在慢性炎症性疾病患者中进行了临床测试，但尚未在移植患者中进行测试。器官移植提供了在器官获取前或冷藏期间开始预处理的机会，从而调节IR损伤的早期事件。未来的研究将需要评估联合策略，包括p38 MAPK和/或JNK抑制，ERK 1/2激活，预处理或后处理方案，新的存储解决方案，和温和的再灌注。
In solid organ transplantation, ischemia/reperfusion (IR) injury during organ procurement, storage and reperfusion is an unavoidable detrimental event for the graft, as it amplifies graft inflammation and rejection. Intracellular mitogen-activated protein kinase (MAPK) signaling pathways regulate inflammation and cell survival during IR injury. The four best-characterized MAPK subfamilies are the c-Jun NH2-terminal kinase (JNK), extracellular signal- regulated kinase-1/2 (ERK1/2), p38 MAPK, and big MAPK-1 (BMK1/ERK5). Here, we review the role of MAPK activation during myocardial IR injury as it occurs during heart transplantation. Most of our current knowledge regarding MAPK activation and cardioprotection comes from studies of preconditioning and postconditioning in nontransplanted hearts. JNK and p38 MAPK activation contributes to myocardial IR injury after prolonged hypothermic storage. p38 MAPK inhibition improves cardiac function after cold storage, rewarming and reperfusion. Small-molecule p38 MAPK inhibitors have been tested clinically in patients with chronic inflammatory diseases, but not in transplanted patients, so far. Organ transplantation offers the opportunity of starting a preconditioning treatment before organ procurement or during cold storage, thus modulating early events in IR injury. Future studies will need to evaluate combined strategies including p38 MAPK and/or JNK inhibition, ERK1/2 activation, pre- or postconditioning protocols, new storage solutions, and gentle reperfusion.