The discovery of angiotensin‐converting enzyme 2 and its role in acute lung injury in mice

Abstract

During several months of 2002, severe acute respiratory syndrome (SARS) caused by SARScoronavirus (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 angiotensinconverting 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.

Angiotensin-Converting Enzyme 2 Inhibits Apoptosis of Pulmonary Endothelial Cells During Acute Lung Injury Through Suppressing MiR-4262

“…ACE2 is the homolog of ACE but counterbalances the ACE activity through induction of degradation of Ang II [5]. Recently, we and others have shown that ACE2 has therapeutic effects on ALI, at least partially through suppression of apoptosis of PECs [6][7][8][9][10].…”

“…Angiotensin-converting enzyme 2 (ACE2) belongs to the renin-angiotensin system [5], in which renin induces the production of angiotensin I (Ang I), which is converted to an important vasoconstrictive peptide Ang II by Ang I-converting enzyme (ACE) [5]. ACE2 is the homolog of ACE but counterbalances the ACE activity through induction of degradation of Ang II [5].…”

Loss of Angiotensin-converting enzyme-related (ACER) peptidase disrupts night-time sleep in adult Drosophila melanogaster

“…ACE2 is highly expressed in the kidney and is also found at lower levels in many other tissues including the heart, testis, liver and lung. ACE2 in the lung, where it is co-expressed with other components of the RAS, has been implicated in the progression of several pulmonary diseases and has been found to have a protective role in murine models of acute respiratory distress syndrome through negative regulation of angiotensin II signalling (Imai et al, 2005;Imai et al, 2008).…”

Another Ace up the Sleeve

“…1). The RAAS later proved to be much more complex than originally thought: the pulmonary vascular endothelium uses angiotensin-converting enzyme 2 (ACE2) to degrade vasoconstrictive Ang II to Ang (1-7), a short-lived potent vasodilator in the pulmonary vascular bed [1,2]. This in turn indicates that besides the well-known vasoconstrictive leg, there is also a vasodilative leg of the RAAS (fig.…”

“…During the past decade, a wealth of research on the biological functions of ACE2 has been performed and there have been some truly amazing findings. For instance, ACE2 may attenuate acute respiratory distress syndrome [2], and has proved to be responsible for cardiac contractility [3] as shown in rodent models. These two studies are of particular interest to the readership of this journal, as the respective authors demonstrate that ACE2 is involved in the regulation of the pulmonary arterial tone and is essential for heart function in vivo.…”