PubMed Journals: Exp Physiol
Source: PMID: 18448662
⇦ ⇨ Exp Physiol. 2008 May;93(5):543-8. doi:
⇩ 10.1113/expphysiol.2007.040048. Epub 2008
The discovery of angiotensin-converting enzyme 2
and its role in acute lung injury in mice.
Imai Y(1), Kuba K, Penninger JM.
(1) The Global Center of Excellence program,
Akita University Graduate School of Medicine,
Akita 010-8543, Japan.
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, termed
angiotensin-converting enzyme 2 (ACE2), has
been identified as a receptor for SARS-CoV.
Angiotensin-converting enzyme and ACE2 share
homology in their catalytic domain and provide
different key functions in the renin-angiotensin system
(RAS). Angiotensin-converting enzyme cleaves
angiotensin I to generate angiotensin II,
which 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,
which can be attenuated by blocking the
renin-angiotensin pathway, suggesting that
the activation of the pulmonary RAS influences
the pathogenesis of ALI/ARDS and SARS.
DOI: 10.1113/expphysiol.2007.040048 PMID: 18448662
[Indexed for MEDLINE]