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|
|Date of Publication (YYYY-MM-DD):||2007-02|
|Title of Journal:||Arteriosclerosis, Thrombosis, and Vascular Biology|
|Journal Abbrev.:||Arterioscler Thromb Vasc Biol|
|Issue / Number:||2|
|Copyright:||© 2007 American Heart Association, Inc.|
|Review Status:||not specified|
|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|
|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
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