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Angiotensin-converting enzyme 2 protects from severe acute lung failure.
Nature. 2005 Jul 07; 436(7047):112-6.Nat

Abstract

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 1-3). 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.

Authors+Show Affiliations

IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna A-1030, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16001071

Citation

Imai, Yumiko, et al. "Angiotensin-converting Enzyme 2 Protects From Severe Acute Lung Failure." Nature, vol. 436, no. 7047, 2005, pp. 112-6.
Imai Y, Kuba K, Rao S, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005;436(7047):112-6.
Imai, Y., Kuba, K., Rao, S., Huan, Y., Guo, F., Guan, B., Yang, P., Sarao, R., Wada, T., Leong-Poi, H., Crackower, M. A., Fukamizu, A., Hui, C. C., Hein, L., Uhlig, S., Slutsky, A. S., Jiang, C., & Penninger, J. M. (2005). Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature, 436(7047), 112-6.
Imai Y, et al. Angiotensin-converting Enzyme 2 Protects From Severe Acute Lung Failure. Nature. 2005 Jul 7;436(7047):112-6. PubMed PMID: 16001071.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin-converting enzyme 2 protects from severe acute lung failure. AU - Imai,Yumiko, AU - Kuba,Keiji, AU - Rao,Shuan, AU - Huan,Yi, AU - Guo,Feng, AU - Guan,Bin, AU - Yang,Peng, AU - Sarao,Renu, AU - Wada,Teiji, AU - Leong-Poi,Howard, AU - Crackower,Michael A, AU - Fukamizu,Akiyoshi, AU - Hui,Chi-Chung, AU - Hein,Lutz, AU - Uhlig,Stefan, AU - Slutsky,Arthur S, AU - Jiang,Chengyu, AU - Penninger,Josef M, PY - 2005/02/11/received PY - 2005/04/29/accepted PY - 2005/7/8/pubmed PY - 2005/7/20/medline PY - 2005/7/8/entrez SP - 112 EP - 6 JF - Nature JO - Nature VL - 436 IS - 7047 N2 - 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 1-3). 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/16001071/full_citation L2 - https://doi.org/10.1038/nature03712 DB - PRIME DP - Unbound Medicine ER -