title: Recombinant Expression and Characterization of Human and Murine ACE2: Species-Specific Activation of the Alternative Renin-Angiotensin-System.
abstract: Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase of the renin-angiotensin-system (RAS) which is known to cleave several substrates among vasoactive peptides. Its preferred substrate is Angiotensin II, which is tightly involved in the regulation of important physiological functions including fluid homeostasis and blood pressure. Ang 1-7, the main enzymatic product of ACE2, became increasingly important in the literature in recent years, as it was reported to counteract hypertensive and fibrotic actions of Angiotensin II via the MAS receptor. The functional connection of ACE2, Ang 1-7, and the MAS receptor is also referred to as the alternative axis of the RAS. In the present paper, we describe the recombinant expression and purification of human and murine ACE2 (rhACE2 and rmACE2). Furthermore, we determined the conversion rates of rhACE2 and rmACE2 for different natural peptide substrates in plasma samples and discovered species-specific differences in substrate specificities, probably leading to functional differences in the alternative axis of the RAS. In particular, conversion rates of Ang 1-10 to Ang 1-9 were found to be substantially different when applying rhACE2 or rmACE2 in vitro. In contrast to rhACE2, rm ACE2 is substantially less potent in transformation of Ang 1-10 to Ang 1-9.
authors.affiliation: APEIRON Biologics AG, Campus-Vienna-Biocenter 5, 1030 Vienna, Austria.
authors.forename: Marko
authors.initials: M
authors.lastname: Poglitsch
authors.forename: Oliver
authors.initials: O
authors.lastname: Domenig
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schwager
authors.forename: Stefan
authors.initials: S
authors.lastname: Stranner
authors.forename: Bernhard
authors.initials: B
authors.lastname: Peball
authors.forename: Evelyne
authors.initials: E
authors.lastname: Janzek
authors.forename: Bettina
authors.initials: B
authors.lastname: Wagner
authors.forename: Helmut
authors.initials: H
authors.lastname: Jungwirth
authors.forename: Hans
authors.initials: H
authors.lastname: Loibner
authors.forename: Manfred
authors.initials: M
authors.lastname: Schuster