The ubiquitous role of nitric oxide in cardioprotection
The ubiquitous role of nitric oxide in cardioprotection
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DOI：
10.1016/j.yjmcc.2005.09.011
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发表时间：
2006-01-01
影响因子：
5
通讯作者：
Bolli, R
中科院分区：
文献类型：
--
作者：
Jones, SP;Bolli, R
近年来，在了解一氧化氮（NO）在心脏缺血生物学中的作用方面取得了重大进展。现在已经清楚的是，无论是内源性还是外源性的NO，都是对抗心肌缺血-再灌注损伤的最重要的防御机制之一。本综述的目的是提供一个更新的心脏保护作用的NO，特别强调的功能的诱导型异构体的NO合酶（iNOS）和线粒体的作用在NO介导的保护。这篇文章强调了一些与NO相关的缺血生物学的突出领域，如缺血预处理，药理学心脏保护和基因治疗。本课题组首次提出的预处理后期是由iNOS活性增加介导的，导致NO生物利用度增加的假说，现已被广泛接受，并被认为是一个已被证实的假说。同样，后调节的新兴领域可能也需要NO。各种药物（例如他汀类药物、ACE抑制剂、血管紧张素受体阻滞剂等）在心肌梗塞的实验模型中也产生有益健康的作用，通过它们增强NO的生物利用度。因此，NO似乎是一种常见的介质的保护提供了一系列看似无关的药理学和非药理学干预，强调其作为一个无处不在的防御心脏缺血和再灌注的基本作用。这篇综述挑战了传统的观点，即iNOS是有害的，在心肌缺血再灌注，而不是提出的概念，即iNOS，在心肌细胞中表达时，是一个深刻的保护蛋白。我们还强调新出现的重要性的线粒体行动的NO。虽然精确的分子事件仍有待定义，我们建议，NO与电子传递链和/或线粒体通透性转换孔的组件相互作用，以限制缺血后心肌损伤，这种行动可能提供了一个基本的分子解释NO介导的心脏保护机制。(c)2005爱思唯尔有限公司保留所有权利。
In recent years, major advances have been made toward understanding the role of nitric oxide (NO) in the ischemic biology of the heart. It is now clear that NO, either endogenous or exogenous, represents one of the most important defenses against myocardial ischemia-reperfusion injury. The purpose of this review is to provide an update on the cardioprotective actions of NO, with particular emphasis on the function of the inducible isoform of NO synthase (iNOS) and on the role of mitochondria in NO-mediated protection. This essay underscores some of the more prominent areas of ischemic biology that relate to NO, such as ischemic preconditioning, pharmacological cardioprotection, and gene therapy. The hypothesis that the late phase of preconditioning is mediated by increased iNOS activity resulting ill enhanced NO bioavailability, first proposed by our group, is now widely accepted and can be regarded as a proven hypothesis. Likewise, the burgeoning field of postconditioning may share such a requirement for NO. Various drugs (e.g. statins, ACE inhibitors, angiotensin-receptor blockers, etc.) also produce salubrious effects in experimental models of myocardial infarction via their enhancement of NO bioavailability. Thus, NO appears to be a common mediator of the protection afforded by a wide array of seemingly unrelated pharmacological and nonpharmacological interventions, underscoring its fundamental role as a ubiquitous defense of the heart against ischemia and reperfusion. This review challenges the conventional wisdom that iNOS is deleterious during myocardial ischemia-reperfusion and instead proposes the concept that iNOS, when expressed in cardiac myocytes, is a profoundly protective protein. We also emphasize the emerging importance of the mitochondrial actions of NO. Although the precise molecular events remain to be defined, we propose that NO interacts with components of the electron transport chain and/or the mitochondrial permeability transition pore to limit post-ischemic myocardial damage, and that this action potentially provides a fundamental molecular explanation for the mechanism of NO-mediated cardioprotection. (c) 2005 Elsevier Ltd. All rights reserved.