[Lessons from SARS: a new potential therapy for acute respiratory distress syndrome (ARDS) with angiotensin converting enzyme 2 (ACE2)].
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). 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.
Imai
Yumiko
Y
Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Austria.
Kuba
Keiji
K
Penninger
Josef M
JM
D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D003001:Cloning, Molecular; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D007703:Peptidyl-Dipeptidase A / Q000172:deficiency / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use*; D011991:Receptors, Virus; D012084:Renin-Angiotensin System / Q000502:physiology; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000209:etiology; D045473:Severe acute respiratory syndrome-related coronavirus; D045169:Severe Acute Respiratory Syndrome / Q000821:virology
D011991:Receptors, Virus; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2