Mann Douglas L, Topkara Veli K, Evans Sarah, Barger Philip M
Division of Cardiology, 660 S. Euclid Ave, Campus Box 8086, St. Louis, MO 63110, USA.
Trans Am Clin Climatol Assoc. 2010;121:34-50; discussion 50-1.
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, and 6. 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 may be 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. Taken together, these new observations provide provisional evidence that the innate immune system is activated in human heart failure, raising the interesting possibility that this pathway may represent a target for the development of novel heart failure therapeutics.
最近的研究表明，心脏拥有一个内在系统，旨在限制组织损伤，并协调心脏内的稳态反应。现有文献表明，这种内在应激反应至少部分是由属于先天免疫系统的一类模式识别受体介导的，包括CD14（脂多糖的可溶性模式识别受体）以及Toll样受体-2、3、4和6。尽管这种内在应激反应系统为组织损伤提供了短期适应性反应，但如果这些分子在心肌中的表达持续存在和/或过度，这个进化上古老的系统的有益作用可能会丧失，在这种情况下，这些途径激活的有益效果可能会被炎症信号已知的有害作用所抵消。在此，我们展示了关于衰竭人类心脏中先天免疫基因表达激活的新信息。综上所述，这些新观察结果提供了初步证据，表明先天免疫系统在人类心力衰竭中被激活，这增加了一个有趣的可能性，即该途径可能代表新型心力衰竭治疗方法开发的一个靶点。
