Angiotensin-converting enzyme 2 protects from severe acute lung failure

By Y. Imai, K. Kuba, Shuan Rao, Yi Huan, F. Guo, Bin Guan, Peng‐fei Yang, R. Sarao, T. Wada, H. Leong-Poi and 8 more. Nature, 2005

2,416 citations recorded by the source corpus.

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.

Subfields: Cardiology and Cardiovascular Medicine, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a78ecf277e9093f3d7dc2cef204faee3059a06cd

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Citations in the corpus

Acute lung injury and the acute respiratory distress syndrome: four decades of inquiry into pathogenesis and rational management. (2005, background): “One recent example of this strategy proposed a novel role for angiotensin-converting enzyme 2 in protecting against experimental ALI (98).”
IL-6 in inflammation, autoimmunity and cancer (2020, background): “AngII–AT1R signaling system plays an important role not only in pneumonia but also in ARDS model mice (345), indicating that lung injury itself activates the AngII–AT1R signaling.”
TMPRSS2 and ADAM17 Cleave ACE2 Differentially and Only Proteolysis by TMPRSS2 Augments Entry Driven by the Severe Acute Respiratory Syndrome Coronavirus Spike Protein (2013, background): “Thus, ACE2 expression was shown to protect against experimentally induced lung injury in a mouse model, and evidence for a decreased ACE2 expression in the context of SARS-CoV infection was obtained (37, 38).”
Coronaviruses post-SARS: Update on replication and pathogenesis (2009, background): “ACE2 is postulated to have a protective role in the inflamed lung, and SARS-CoV S protein binding to ACE2 is thought to contribute to disease severit”
ACE-2 expression in the small airway epithelia of smokers and COPD patients: implications for COVID-19 (2020, background): “However, in mice, ACE2 has been shown to protect animals from severe lung injury related to aspiration and sepsis [18].”