Received March 5, 2008
Revised March 13, 2008
Accepted after revision March 13, 2008
The discovery of ACE2 and its role in acute lung injury
Yumiko Imai 1,
Keiji Kuba 2,
Josef Penninger 3*
1 Akita University Graduate School of Medicine,
2 Tokyo Medical and Dental University
3 Austrian Academy of Science
* To whom correspondence should be addressed. E-mail: josef.penninger{at}imba.oeaw.ac.at.
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Abstract |
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During several months of 2002, severe acute respiratory syndrome (SARS) caused by SARS-coronavirus (SARS-CoV) spread rapidly from China throughout the world causing more than 800 deaths due to the development of acute respiratory distress syndrome (ARDS), which is the severe form of acute lung injury (ALI). Interestingly, a novel homologue of angiotensin converting-enzyme (ACE), termed angiotensin converting enzyme 2 (ACE2) has been identified as a receptor for SARS-CoV. ACE and ACE2 share homology in their catalytic domain and provide different key functions in the renin-angiotensin system. ACE cleaves angiotensin I to generate angiotensin II that is a key effector peptide of the system and exerts multiple biological functions, whereas ACE2 reduces angiotensin II levels. Importantly, our recent studies using ACE2 knockout mice have demonstrated that ACE2 protects murine lungs from ARDS. Furthermore, SARS-CoV infections and the Spike protein of the SARS-CoV reduce ACE2 expression. Notably, injection of SARS-CoV Spike into mice worsens acute lung failure in vivo that can be attenuated by blocking the renin-angiotensin pathway, suggesting the activation of pulmonary RAS influences the pathogenesis of ALI/ARDS and SARS.
