Could interferon-gamma be a therapeutic target for treating heart failure?

Could interferon-gamma be a therapeutic target for treating heart failure?
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DOI:
10.1007/s10741-013-9393-8
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发表时间:
2014-03
影响因子:
4.6
通讯作者:
Goldspink, Paul H.
Goldspink, Paul H.
中科院分区:
医学2区
文献类型:
--
作者:
Levick, Scott P.;Goldspink, Paul H.

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细胞因子干扰素-γ是II型干扰素家族中唯一已知的成员,因此,它与自己独特的受体结合。它在宿主抵抗感染和适应性免疫反应中很重要。虽然已知多种细胞因子参与心脏的不良重塑和心力衰竭的进展,但干扰素-γ的作用尚不清楚。最近来自临床研究、心肌炎和高血压的动物模型以及分离细胞研究的证据,提供了关于干扰素-γ在心脏中是病理性的还是保护性的相互矛盾的数据。因此,重要的是要强调这些不同的发现,以便能够确定未来研究的领域,以更清楚地确定干扰素-γ在心脏中的确切作用。因此,该综述将:1)讨论干扰素-γ在疾病心脏中的来源;2)总结动物研究的数据;3)讨论干扰素-γ对分离的心脏成纤维细胞和心肌细胞的影响;4)确定干扰素-γ在心脏中可能激活的信号机制;以及5)提供支持干扰素-γ在心力衰竭中作用的临床证据。
The cytokine interferon-gamma (IFN-γ), is the only known member of the type II family of interferons, and as such, binds to its own distinct receptor. It is important in host defense against infection, as well as adaptive immune responses. Whilst a wide array of cytokines are known to be involved in adverse remodeling of the heart and the progression to heart failure, the role of IFN-γ is unclear. Recent evidence from clinical studies, animal models of myocarditis and hypertension, as well as isolated cell studies, provide conflicting data as to whether IFN-γ is pathological or protective in the heart. Thus, it is important to highlight these discrepant findings so that areas of future investigation can be identified to more clearly determine the precise role of IFN-γ in the heart. Accordingly, this review will: 1) discuss the source of IFN-γ in the diseased heart; 2) summarize the data from animal studies; 3) discuss the effects of IFN-γ on isolated cardiac fibroblasts and cardiomyocytes; 4) identify signaling mechanisms that may be invoked by IFN-γ in the heart; and 5) present the clinical evidence supporting a role for IFN-γ in heart failure.
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