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  Mass-spectrometric identification of a novel angiotensin peptide in human plasma

Jankowski, V., Vanholder, R., van der Giet, M., Tölle, M., Karadogan, S., Gobom, J., et al. (2007). Mass-spectrometric identification of a novel angiotensin peptide in human plasma. Arteriosclerosis, Thrombosis, and Vascular Biology, 27(2), 297-302. doi:10.1161/01.ATV.0000253889.09765.5f.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8262-E Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8263-C
Genre: Journal Article
Alternative Title : Arterioscler Thromb Vasc Biol

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 Creators:
Jankowski, Vera, Author
Vanholder, Raymond, Author
van der Giet, Markus, Author
Tölle, Markus, Author
Karadogan, Sevil, Author
Gobom, Johan1, Author              
Furkert, Jens, Author
Oksche, Alexander, Author
Krause, Eberhard, Author
Tran, Thi Nguyet Anh, Author
Tepel, Martin, Author
Schuchardt, Mirjam, Author
Schlüter, Hartmut, Author
Wiedon, Annette, Author
Beyermann, Michael, Author
Bader, Michael, Author
Todiras, Mihail, Author
Zidek, Walter, Author
Jankowski, Joachim, Author
Affiliations:
1Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              

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Free keywords: mass-spectrometry; vasoconstriction; angiotensin-peptide; human plasma
 Abstract: 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.

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Language(s): eng - English
 Dates: 2007-02
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Degree: -

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Title: Arteriosclerosis, Thrombosis, and Vascular Biology
  Alternative Title : Arterioscler Thromb Vasc Biol
Source Genre: Journal
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Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 27 (2) Sequence Number: - Start / End Page: 297 - 302 Identifier: ISSN: 1079-5642