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

Wysocki, Jan; Schulze, Arndt; Batlle, Daniel

The lack of increase in urinary ACE2 activity after injection of native rACE2 was attributed to the lack of glomerular filtration of native rACE2, consistent with its large molecular size of 100-110 kDa [12, 13] . While markedly increased circulatory levels of ACE2 activity after native rACE2 administration are capable of effectively lowering blood pressure in models of Ang II-induced hypertension [6, 7, 14] or renin overexpression in the circulation [15] , their use is not suitable for treatment of other forms of kidney disease. For instance, in a diabetic model with local kidney but not systemic RAS over-activity [13] , long-term augmentation of circulating ACE2 activity was not sufficient to alter glomerular pathology, GFR or albuminuria [13] . These observations provide the rationale for the development of shorter forms of ACE2 with a molecular size that render them filtrable by the kidney and, therefore, potentially useful therapeutically to amplify ACE2 activity in forms of kidney disease with an overactive local RAS in the kidney [13, 16] .