Role of nitric oxide in myocardial preconditioning
Role of nitric oxide in myocardial preconditioning
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DOI：
10.1111/j.1749-6632.2002.tb04053.x
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发表时间：
2002-01-01
期刊：
影响因子：
--
通讯作者：
Bolli, R
中科院分区：
文献类型：
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作者：
Dawn, B;Bolli, R
缺血预处理（PC）是一种多基因防御性细胞适应现象，通过短暂的缺血刺激使心脏抵抗随后类似的应激。缺血PC的晚期持续3 ~ 4天，对心肌昏迷和梗死都有保护作用，因此具有相当大的临床意义。亚致死缺血应激释放的多种信号分子启动了一个复杂的信号转导级联，调节心脏保护基因的表达。一氧化氮（NO）由内皮NO合成酶（NOS）产生，通过活性氧的形成，激活蛋白激酶C （PKC）的E亚型，从而激活蛋白酪氨酸激酶Src家族（Src和Lck）和转录因子（核因子- kappab，可能还有其他），从而导致诱导的NOS （iNOS）基因和蛋白表达上调。iNOS和其他心脏保护蛋白，包括环氧化酶-2和醛糖还原酶，赋予对随后的缺血应激的抵抗力。这种延迟保护也可以模仿，在没有缺血的情况下，通过施用no释放剂，这种情况可以潜在地用于临床情况下的心脏保护。发现一氧化氮在心脏保护中的这种新的双功能（触发和中介）作用，不仅提高了对其信号功能的认识，而且为冠状动脉疾病患者提供了潜在的治疗策略。本综述的目的是总结目前支持一氧化氮在缺血性PC中发挥关键作用的证据。
Ischemic preconditioning (PC) is a polygenic defensive cellular adaptive phenomenon whereby brief ischemic stimuli render the heart resistant to subsequent similar stress. The late phase of ischemic PC lasts for three to four days, protects against both myocardial stunning and infarction, and thus has considerable clinical relevance. Diverse signaling molecules released by a sublethal ischemic stress initiate a complex signal transduction cascade that modulates the expression of cardioprotective genes. Nitric oxide (NO), generated by the endothelial NO synthase (NOS) and acting via the formation of reactive oxygen species, activates the E isoform of protein kinase C (PKC), which activates the Src family of protein tyrosine kinases (Src and Lck) and transcription factors (nuclear factor-kappaB, and possibly others), with resultant upregulation of the inducible NOS (iNOS) gene and protein expression. iNOS, and other cardioprotective proteins, including cyclooxygenase-2 and aldose reductase, confer resistance to subsequent ischemic stress. This delayed protection can also be mimicked, in the absence of ischemia, by administering NO-releasing agents, a situation that can be potentially exploited for cardioprotection in clinical situations. Identification of this novel bifunctional (trigger and mediator) role played by NO in cardiac protection, not only advances the knowledge regarding its signaling functions, but also offers a potential therapeutic strategy for patients with coronary artery disease. The purpose of this review is to summarize the current evidence in support of this critical role played by NO in ischemic PC.