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

Wysocki, Jan; Schulze, Arndt; Batlle, Daniel

Knowing that the kidney ACE2 activity can be increased by the administration of short ACE2 variants, the natural question is under what clinical conditions such kidney amplification could be useful. We speculate that disease conditions where the local kidney RAS is over-active would be the natural target. Several studies using diabetic models show activation of the RAS locally within the kidney by glucose, including an increase in Ang II production [33] [34] [35] [36] . Additional evidence comes from findings of increased RAS components in the kidney and urines from rodent models of diabetic kidney disease (DKD) and in patients with DKD [16, 37] and non-diabetic CKD [38, 39] . There is a need for new approaches to counteract RAS overactivity that expand and improve on the existing ones which are based on blockade of Ang II formation or action. We have chosen ACE2 as a therapeutic target because this enzyme cleaves Ang II to form Ang (1-7) with the highest efficiency [6, 26, 40] .