In comparison with serum ACE, Rice and colleagues reported that the circulating levels of ACE2 were 100-fold lower and that <10% (40 out of 494) of their patients expressed measurable ACE2 activity [3] . Nevertheless, families with detectable circulating ACE2 exhibited a greater incidence of cardiovascular pathologies although the overall sample population was low. More recent studies by Epelman and colleagues fi nd that circulating levels of ACE2 are highly associated with increasing severity of progressive heart failure [4] . However, patients