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

Wysocki, Jan; Schulze, Arndt; Batlle, Daniel

Angiotensin Converting Enzyme-2 (ACE2) is a monocarboxypeptidase that degrades several substrates, of which Ang II is most relevant because of the extensive biologic effects of this peptide and the attendant formation of Ang (1-7), which has actions generally opposite to those of Ang II [1] [2] [3] [4] [5] [6] [7] [8] [9] . ACE2 protein in its full-length form is an 805 amino-acid (AA) type-I transmembrane protein (110-120 kDa) that contains an extracellular domain (AA 1-740), a transmembrane region (AA 741-768), and an intracellular tail (769-805) [10, 11] . The extracellular part of ACE2 (1-740 AA), here referred as "native" ACE2, contains the catalytic domain and is fully catalytically active. In our previous studies, the administration of native rACE2 (1-740 AA) resulted in a marked increase in circulating ACE2 activity, but neither kidney nor urinary ACE2 activity increased [6, 12, 13] .