TGF-beta, IL-6, IL-17 and CTGF direct multiple pathologies of chronic cardiac allograft rejection.
TGF-beta, IL-6, IL-17 and CTGF direct multiple pathologies of chronic cardiac allograft rejection.
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DOI：
10.2217/imt.10.33
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发表时间：
2010-07
期刊：
影响因子：
2.8
通讯作者：
Bishop DK
中科院分区：
文献类型：
--
作者：
Booth AJ;Bishop DK
心脏移植是治疗顽固性心力衰竭的有效方法。尽管免疫抑制治疗提高了第一年的存活率，但慢性排斥反应仍然是移植物长期存活的重要障碍。慢性排斥反应表现为斑片状间质纤维化、血管闭塞和移植物功能的进行性丧失。最近来自实验和患者研究的证据表明，心肌细胞肥大的发展是慢性心脏移植排斥反应的另一个标志。这种病理性肥大与免疫细胞因子IL-6密切相关，IL-6与TGF-β和IL-17一起促进慢性排斥反应的各个方面。这些因子增强下游介质，如CTGF，其促进与疾病相关的纤维化。在本文中，我们总结了当代的研究结果，这些研究结果揭示了与心脏移植慢性排斥反应的诱导和进展有关的几个因素。进一步努力阐明这些因素之间的相互作用可能会指导这种疾病的靶向治疗的发展。
Cardiac transplantation is an effective treatment for heart failure refractive to therapy. Although immunosuppressive therapeutics have increased first year survival rates, chronic rejection remains a significant barrier to long-term graft survival. Chronic rejection manifests as patchy interstitial fibrosis, vascular occlusion and progressive loss of graft function. Recent evidence from experimental and patient studies suggests that the development of cardiomyocyte hypertrophy is another hallmark of chronic cardiac allograft rejection. This pathologic hypertrophy is tightly linked to the immune cytokine IL-6, which promotes facets of chronic rejection in concert with TGF-β and IL-17. These factors potentiate downstream mediators, such as CTGF, which promote the fibrosis associated with the disease. In this article, we summarize contemporary findings that have revealed several elements involved in the induction and progression of chronic rejection of cardiac allografts. Further efforts to elucidate the interplay between these factors may direct the development of targeted therapies for this disease.