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Review
. 2006 Oct;84(10):814-20.
doi: 10.1007/s00109-006-0094-9. Epub 2006 Sep 19.

Lessons from SARS: control of acute lung failure by the SARS receptor ACE2

Keiji Kuba  1 , Yumiko Imai, Shuan Rao, Chengyu Jiang, Josef M Penninger
Affiliations
Review

Lessons from SARS: control of acute lung failure by the SARS receptor ACE2

Keiji Kuba et al. J Mol Med (Berl). 2006 Oct.

Abstract

Angiotensin-converting enzyme 2 (ACE2), a second angiotensin-converting enzyme (ACE), regulates the renin-angiotensin system by counterbalancing ACE activity. Accumulating evidence in recent years has demonstrated a physiological and pathological role of ACE2 in the cardiovascular systems. Recently, it has been shown that severe acute respiratory syndrome (SARS) coronavirus, the cause of SARS, utilizes ACE2 as an essential receptor for cell fusion and in vivo infections in mice. Intriguingly, ACE2 acts as a protective factor in various experimental models of acute lung failure and, therefore, acts not only as a key determinant for SARS virus entry into cells but also contributes to SARS pathogenesis. Here we review the role of ACE2 in disease pathogenesis, including lung diseases and cardiovascular diseases.

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Figures

Fig. 1
Fig. 1
Current view of ACE and ACE2 functions. ANG I (DRVYIHPFHL) serves as a substrate for both ACE and ACE2. ANG II (DRVYIHPF) is known to act as vasoconstrictor in vivo. The function of angiotensin 1–9 (DRVYIHPFH) is not well understood. Both ACE and ACE2 are involved in the production of the vasodilator peptide angiotensin 1–7 (DRVYIHPF). Red arrowheads ACE cleavage site; blue arrowheads ACE2 cleavage sites. It should be noted that ACE2 is an unspecific protease and can cleave multiple additional substrates, such as apelin
Fig. 2
Fig. 2
Schematic diagram of the role of the RAS in acute lung failure and proposed SARS-CoV action. In acute lung injury, such as acid aspiration, pneumonia, or sepsis, the generation of ANG II from ANG I is enhanced by ACE, and ANG II induces acute lung failure through stimulation of the AT1 receptor, while ACE2 and ANG II type 2 receptor negatively regulate this pathway and protect from acute lung failure. On the other hand, SARS-CoV infection is mediated through binding of the SARS-Spike protein to ACE2 or L-SIGN and down-regulates the protective molecule ACE2, and thus leads to severe lung injury and acute lung failure
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