Therapeutic targeting of innate immunity in the failing heart.
Therapeutic targeting of innate immunity in the failing heart.
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DOI：
10.1016/j.yjmcc.2010.11.003
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发表时间：
2011-10
影响因子：
5
通讯作者：
Mann DL
中科院分区：
文献类型：
--
作者：
Topkara VK;Evans S;Zhang W;Epelman S;Staloch L;Barger PM;Mann DL
最近的研究表明，心脏拥有一个内在的系统，旨在界定组织损伤，以及协调心脏内的稳态反应。现存的文献表明，这种内在应激反应至少部分地由属于先天免疫系统的模式识别受体家族介导，所述模式识别受体家族包括CD 14（脂多糖的可溶性模式识别受体）和Toll样受体-2，3，4，5，6，7和9。尽管这种内在应激反应系统提供了对组织损伤的短期适应性反应，但是如果这些分子的心肌表达变得持续和/或过度，则这种遗传学上古老的系统的有益作用可能会丧失，在这种情况下，这些途径的激活的有益作用与炎症信号传导的已知有害作用相抵触。在此，我们提出了新的信息，关于激活先天免疫基因表达的人心脏衰竭，以及审查新的TLR拮抗剂，正在开发的其他适应症以外的心力衰竭。这篇综述将讨论TLR通路可能成为开发新型心力衰竭治疗药物的新靶点的可能性。
Recent studies suggest that the heart possesses an intrinsic system that is intended to delimit tissue injury, as well as orchestrate homoeostatic responses within the heart. The extant literature suggests that this intrinsic stress response is mediated, at least in part, by a family of pattern recognition receptors that belong to the innate immune system, including CD14, the soluble pattern recognition receptor for lipopolysaccharide, and Toll like receptors-2, 3, 4, 5, 6, 7 and 9. Although this intrinsic stress response system provides a short-term adaptive response to tissue injury, the beneficial effects of this phylogenetically ancient system may be lost if myocardial expression of these molecules either becomes sustained and/or excessive, in which case the salutary effects of activation of these pathways is contravened by the known deleterious effects of inflammatory signaling. Herein we present new information with regard to activation of innate immune gene expression in the failing human heart, as well as review the novel TLR antagonists that are being developed for other indications outside of heart failure. This review will discuss the interesting possibility that the TLR pathway may represent a new target for the development of novel heart failure therapeutics.
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1161/atvbaha.107.140723
发表时间：
2007-05-01
影响因子：
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