Good ACE, bad ACE do battle in lung injury, SARS

Abstract

Two studies show how the enzyme ACE2 protects against lung injury caused by SARS and other agents. ACE2 seems to counteract the effects of ACE, which are more damaging (pages 875–879).

Figure 1. Simplified schematic representation of angiotensin-converting enzyme (ACE) regulation of acute lung injury.

ACE converts angiotensin I (AT I) to angiotensin II (AT II) which binds to either angiotensin II receptor 1a (AT1aR), leading to tissue damage and lung edema, or to angiotensin II receptor 2 (AT2R), reducing tissue damage. Angiotensin-converting enzyme 2 (ACE2) in turn converts the potent AT II to a less damaging angiotensin_1–7 (AT_1–7). SARS binds to ACE2, resulting in downregulation through its internalization, and thus reduced inactivation of AT II. Lipopolysaccharide, sepsis and acid treatment also results in ACE2 downregulation. Administration of recombinant ACE2 (rACE2) reduces lung damage by inactivation of AT II and treatment with AT1aR antagonists (ATA) may also have the potential to reduce lung damage. Katie Ris