• Yumiko Imai, Keiji Kuba, and Josef M Penninger.
• Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Austria.
• Masui. 2008 Mar 1; 57 (3): 302-10.

AbstractDuring 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). 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 and thus is a negative regulator of the system. 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 ARDS and SARS.

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