Recombinant Expression and Characterization of Human and Murine ACE2: Species-Specific Activation of the Alternative Renin-Angiotensin-System. (28th February 2012)

• Record Type: Journal Article
• Authors: Poglitsch, Marko; Domenig, Oliver; Schwager, Cornelia; Stranner, Stefan; Peball, Bernhard; Janzek, Evelyne; Wagner, Bettina; Jungwirth, Helmut; Loibner, Hans; Schuster, Manfred
• Other Names: Ferreira Anderson J. Academic Editor.
• Is Part Of: International journal of hypertension. Volume 2012(2012)
• Publication Date: 2012-02-28
• Subjects: Hypertension -- Periodicals; Hypertension; Hypertension; Periodicals; 616.132005
• DOI: 10.1155/2012/428950
• Languages: English
• ISSNs: 2090-0384

Abstract

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.