Angiotensin-converting enzyme 2 protects from severe acute lung failure.
Angiotensin-converting enzyme 2 protects from severe acute lung failure.
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DOI：
10.1038/nature03712
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发表时间：
2005-07-07
期刊：
影响因子：
64.8
通讯作者：
Penninger JM
中科院分区：
文献类型：
--
作者：
Imai Y;Kuba K;Rao S;Huan Y;Guo F;Guan B;Yang P;Sarao R;Wada T;Leong-Poi H;Crackower MA;Fukamizu A;Hui CC;Hein L;Uhlig S;Slutsky AS;Jiang C;Penninger JM
2003年的SARS（严重急性呼吸综合征）疫情造成近800人死亡，其中许多人是由于急性呼吸窘迫综合征（ARDS）的并发症。目前还没有有效的药物可用于治疗ARDS，但小鼠的新研究表明，ACE 2（血管紧张素转换酶2）可能是一种选择。ACE 2可以保护小鼠免受ARDS样综合征的肺损伤，而用于控制血压和盐平衡的肾素-血管紧张素系统的其他成分实际上使病情恶化。ACE 2在健康肺中表达，但被肺损伤下调，并且最近显示（Nature 426，450-454; 2003）它是SARS冠状病毒的受体。本文的在线版本（doi：10.1038/nature 03712）包含补充材料，可供授权用户使用。急性呼吸窘迫综合征（acute respiratory distress syndrome，ARDS）是急性肺损伤中最严重的一种，是一种严重的临床综合征，死亡率高（30-60%）。ARDS的诱发因素多种多样，包括败血症、吸入性肺炎和严重急性呼吸综合征（SARS）冠状病毒感染。目前尚无有效的药物改善ARDS的临床结局。血管紧张素转换酶（ACE）和ACE 2是在肾素-血管紧张素系统中具有不同关键功能的同源物。ACE切割血管紧张素I以产生血管紧张素II，而ACE 2使血管紧张素II失活并且是该系统的负调节剂。ACE 2最近也被鉴定为潜在的SARS病毒受体，并在肺中表达。在这里，我们报告，ACE 2和血管紧张素II 2型受体（AT 2）保护小鼠免受严重急性肺损伤酸吸入或败血症。然而，肾素-血管紧张素系统的其他组分，包括ACE、血管紧张素II和血管紧张素II 1a型受体（AT 1a），促进疾病发病机制，诱导肺水肿和损害肺功能。我们发现，缺乏ACE的小鼠表现出显着改善的疾病，而且重组ACE 2可以保护小鼠免受严重的急性肺损伤。我们的数据确定了ACE 2在急性肺损伤中的关键功能，为每年影响全球数百万人的综合征提供了可能的治疗方法。本文的在线版本（doi：10.1038/nature 03712）包含补充材料，可供授权用户使用。
The SARS (severe acute respiratory syndrome) epidemic of 2003 caused almost 800 deaths, many of them due to acute respiratory distress syndrome (ARDS) as a complication. There are no effective drugs available for treating ARDS, but new work in mice suggests that ACE2 (angiotensin-converting enzyme 2) might be an option. ACE2 can protect mice from lung injury in an ARDS-like syndrome, whereas other components of the renin–angiotensin system for controlling blood pressure and salt balance actually make the condition worse. ACE2 is expressed in the healthy lung but downregulated by lung injury and it was shown recently (Nature 426, 450–454; 2003) to be a receptor for the SARS coronavirus. The online version of this article (doi:10.1038/nature03712) contains supplementary material, which is available to authorized users. Acute respiratory distress syndrome (ARDS), the most severe form of acute lung injury, is a devastating clinical syndrome with a high mortality rate (30–60%) (refs). Predisposing factors for ARDS are diverse and include sepsis, aspiration, pneumonias and infections with the severe acute respiratory syndrome (SARS) coronavirus. At present, there are no effective drugs for improving the clinical outcome of ARDS. Angiotensin-converting enzyme (ACE) and ACE2 are homologues with different key functions in the renin–angiotensin system. ACE cleaves angiotensin I to generate angiotensin II, whereas ACE2 inactivates angiotensin II and is a negative regulator of the system. ACE2 has also recently been identified as a potential SARS virus receptor and is expressed in lungs. Here we report that ACE2 and the angiotensin II type 2 receptor (AT2) protect mice from severe acute lung injury induced by acid aspiration or sepsis. However, other components of the renin–angiotensin system, including ACE, angiotensin II and the angiotensin II type 1a receptor (AT1a), promote disease pathogenesis, induce lung oedemas and impair lung function. We show that mice deficient for Ace show markedly improved disease, and also that recombinant ACE2 can protect mice from severe acute lung injury. Our data identify a critical function for ACE2 in acute lung injury, pointing to a possible therapy for a syndrome affecting millions of people worldwide every year. The online version of this article (doi:10.1038/nature03712) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
影响因子：
64.8
作者：
HEIN, L;BARSH, GS;KOBILKA, BK
通讯作者：
KOBILKA, BK
影响因子：
7.3
作者：
Hamming, I;Timens, W;van Goor, H
通讯作者：
van Goor, H
影响因子：
64.8
作者：
Crackower, MA;Sarao, R;Penninger, JM
通讯作者：
Penninger, JM
DOI：
10.1164/rccm.2108086
发表时间：
2002-09-01
影响因子：
24.7
作者：
Marshall, RP;Webb, S;Laurent, GJ
通讯作者：
Laurent, GJ