Novel Variants of Angiotensin Converting Enzyme-2 of Shorter Molecular Size to Target the Kidney Renin Angiotensin System

Wysocki, Jan; Schulze, Arndt; Batlle, Daniel

We next proceeded to demonstrate that longer exposure of the 110 kDa native rACE2 to proteases from kidneys resulted in the formation of even a shorter~60-70 kDa band and showed that it still had very high ACE2 enzymatic activity (Figure 1 ). By contrast, in the urine, extended incubation of native rACE2 ultimately led to the disappearance of the 75 kDa ACE2 band and a loss of ACE2 activity. This suggests that, unlike the kidney, in which ACE2 truncates can prevail for an extended period of time, the urine is equipped with a repertoire of proteases that inactivate ACE2 by digesting it to small inactive fragments. We did not investigate, however, the specific proteases responsible for the cleavage of ACE2 or the cleavage site. Such studies should be done in the future.