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ID: 334817.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
Mass-spectrometric identification of a novel angiotensin peptide in human plasma
Authors:Jankowski, Vera; Vanholder, Raymond; van der Giet, Markus; Tölle, Markus; Karadogan, Sevil; Gobom, Johan; Furkert, Jens; Oksche, Alexander; Krause, Eberhard; Tran, Thi Nguyet Anh; Tepel, Martin; Schuchardt, Mirjam; Schlüter, Hartmut; Wiedon, Annette; Beyermann, Michael; Bader, Michael; Todiras, Mihail; Zidek, Walter; Jankowski, Joachim
Language:English
Date of Publication (YYYY-MM-DD):2007-02
Title of Journal:Arteriosclerosis, Thrombosis, and Vascular Biology
Journal Abbrev.:Arterioscler Thromb Vasc Biol
Volume:27
Issue / Number:2
Start Page:297
End Page:302
Copyright:© 2007 American Heart Association, Inc.
Review Status:not specified
Audience:Experts Only
Abstract / Description:Objective— Angiotensin peptides play a central role in cardiovascular physiology and pathology. Among these peptides, angiotensin II (Ang II) has been investigated most intensively. However, further angiotensin peptides such as Ang 1-7, Ang III, and Ang IV also contribute to vascular regulation, and may elicit additional, different, or even opposite effects to Ang II. Here, we describe a novel Ang II-related, strong vasoconstrictive substance in plasma from healthy humans and end-stage renal failure patients.

Methods and Results— Chromatographic purification and structural analysis by matrix-assisted laser desorption/ionisation time-of-flight/time-of-flight (MALDI-TOF/TOF) revealed an angiotensin octapeptide with the sequence Ala-Arg-Val-Tyr-Ile-His-Pro-Phe, which differs from Ang II in Ala1 instead of Asp1. Des[Asp1]-[Ala1]-Ang II, in the following named Angiotensin A (Ang A), is most likely generated enzymatically. In the presence of mononuclear leukocytes, Ang II is converted to Ang A by decarboxylation of Asp1. Ang A has the same affinity to the AT1 receptor as Ang II, but a higher affinity to the AT2 receptor. In the isolated perfused rat kidney, Ang A revealed a smaller vasoconstrictive effect than Ang II, which was not modified in the presence of the AT2 receptor antagonist PD 123319, suggesting a lower intrinsic activity at the AT1 receptor. Ang II and Ang A concentrations in plasma of healthy subjects and end-stage renal failure patients were determined by matrix-assisted laser desorption/ionisation mass-analysis, because conventional enzyme immunoassay for Ang II quantification did not distinguish between Ang II and Ang A. In healthy subjects, Ang A concentrations were less than 20% of the Ang II concentrations, but the ratio Ang A / Ang II was higher in end-stage renal failure patients.

Conclusion— Ang A is a novel human strong vasoconstrictive angiotensin-derived peptide, most likely generated by enzymatic transformation through mononuclear leukocyte-derived aspartate decarboxylase. Plasma Ang A concentration is increased in end-stage renal failure. Because of its stronger agonism at the AT2 receptor, Ang A may modulate the harmful effects of Ang II.

In this study, a new angiotensin-peptide of human plasma is described, which is characterized as a strong AT2-receptor agonist.
Free Keywords:mass-spectrometry; vasoconstriction; angiotensin-peptide; human plasma
Comment of the Author/Creator:E-mail: Joachim.Jankowski@charite.de
External Publication Status:published
Document Type:Article
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin Medizinische Klinik IV, Germany;
Department of Internal Medicine, University Hospital, Gent, Belgium;
Charité-Universitätsmedizin Berlin, Institut für Pharmakologie, Germany;
Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany;
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany
Identifiers:ISSN:1079-5642
DOI:10.1161/01.ATV.0000253889.09765.5f
URL:http://atvb.ahajournals.org/cgi/reprint/27/2/297
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