Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections.

Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections.
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血管紧张素转换酶 2 可预防致命的甲型禽流感 H5N1 感染

DOI:
10.1038/ncomms4594
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发表时间:
2014-05-06
影响因子:
16.6
通讯作者:
Jiang C
Jiang C
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Zou Z;Yan Y;Shu Y;Gao R;Sun Y;Li X;Ju X;Liang Z;Liu Q;Zhao Y;Guo F;Bai T;Han Z;Zhu J;Zhou H;Huang F;Li C;Lu H;Li N;Li D;Jin N;Penninger JM;Jiang C

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近年来,禽流感H5 N1爆发的可能性有所增加。因此,制定新的战略来降低死亡率至关重要。在这里,我们表明,禽流感A H5 N1感染的患者表现出显着增加的血清血管紧张素II水平。高血清血管紧张素II水平似乎与感染的严重性和致死性有关,至少在一些患者中是这样。在实验小鼠模型中,感染高致病性甲型禽流感H5 N1病毒导致肺血管紧张素转换酶2(ACE 2)表达下调,血清血管紧张素II水平升高。ACE 2的基因失活导致H5 N1攻击小鼠的严重肺损伤,证实ACE 2在H5 N1诱导的肺病理中的作用。重组人ACE 2的施用改善禽流感H5 N1病毒诱导的小鼠肺损伤。我们的数据将H5 N1病毒诱导的急性肺衰竭与ACE 2联系起来,并为应对未来的流感大流行提供了潜在的治疗策略。本文的在线版本(doi:10.1038/ncomms 4594)包含补充材料,可供授权用户使用。H5 N1禽流感病毒具有高致病性。在这里,作者表明,H5 N1感染导致患者和小鼠血清血管紧张素II水平升高,给予血管紧张素转换酶2可改善感染小鼠的肺损伤。本文的在线版本(doi:10.1038/ncomms 4594)包含补充材料,可供授权用户使用。
The potential for avian influenza H5N1 outbreaks has increased in recent years. Thus, it is paramount to develop novel strategies to alleviate death rates. Here we show that avian influenza A H5N1-infected patients exhibit markedly increased serum levels of angiotensin II. High serum levels of angiotensin II appear to be linked to the severity and lethality of infection, at least in some patients. In experimental mouse models, infection with highly pathogenic avian influenza A H5N1 virus results in downregulation of angiotensin-converting enzyme 2 (ACE2) expression in the lung and increased serum angiotensin II levels. Genetic inactivation of ACE2 causes severe lung injury in H5N1-challenged mice, confirming a role of ACE2 in H5N1-induced lung pathologies. Administration of recombinant human ACE2 ameliorates avian influenza H5N1 virus-induced lung injury in mice. Our data link H5N1 virus-induced acute lung failure to ACE2 and provide a potential treatment strategy to address future flu pandemics. The online version of this article (doi:10.1038/ncomms4594) contains supplementary material, which is available to authorized users. H5N1 avian influenza viruses can be highly pathogenic. Here, the authors show that H5N1 infection leads to increased serum levels of angiotensin II in patients and mice, and that administration of angiotensin-converting enzyme 2 ameliorates lung injury in infected mice. The online version of this article (doi:10.1038/ncomms4594) contains supplementary material, which is available to authorized users.
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