This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 27/2/297    most recent 01.ATV.0000253889.09765.5fv1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jankowski, V. Articles by Jankowski, J. Search for Related Content PubMed PubMed Citation Articles by Jankowski, V. Articles by Jankowski, J. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Compound via MeSH Substance via MeSH

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:297.)
© 2007 American Heart Association, Inc.

Vascular Biology

Mass-Spectrometric Identification of a Novel Angiotensin Peptide in Human Plasma

Vera Jankowski; Raymond Vanholder; Markus van der Giet; Markus Tölle; Sevil Karadogan; Johan Gobom; Jens Furkert; Alexander Oksche; Eberhard Krause; Thi Nguyet Anh Tran; Martin Tepel; Mirjam Schuchardt; Hartmut Schlüter; Annette Wiedon; Michael Beyermann; Michael Bader; Mihail Todiras; Walter Zidek; Joachim Jankowski

From the Charité-Universitätsmedizin Berlin (V.J., M.v.d.G., M.Tölle, S.K., M.Tepel, M.S., H.S., A.W., W.Z., J.J.), Campus Benjamin Franklin Medizinische Klinik IV, Germany; Nephrology Section (R.V.), Department of Internal Medicine, University Hospital, Gent, Belgium; Max Planck Institute for Molecular Genetics (J.G.), Berlin, Germany; Charité-Universitätsmedizin Berlin (J.F., A.O.), Institut für Pharmakologie, Germany; Forschungsinstitut für Molekulare Pharmakologie (E.K., M.Beyermann, M.T.), Berlin, Germany; and Max-Delbrück-Center for Molecular Medicine (M.Bader), Berlin, Germany.

Correspondence to Priv.-Doz. Dr J. Jankowski, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin Med Klinik IV, Hindenburgdamm 30, 12200 Berlin, Germany. E-mail Joachim.Jankowski{at}charite.de

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.

Key Words: mass-spectrometry • vasoconstriction • angiotensin-peptide • human plasma

This article has been cited by other articles:

				R. Vanholder, U. Baurmeister, P. Brunet, G. Cohen, G. Glorieux, J. Jankowski, and for the European Uremic Toxin Work Group A Bench to Bedside View of Uremic Toxins J. Am. Soc. Nephrol., May 1, 2008; 19(5): 863 - 870. [Abstract] [Full Text] [PDF]

				F. Feihl, L. Liaudet, B. I. Levy, and B. Waeber Hypertension and microvascular remodelling Cardiovasc Res, May 1, 2008; 78(2): 274 - 285. [Abstract] [Full Text] [PDF]

				R. Vanholder, S. V. Laecke, F. Verbeke, G. Glorieux, and W. V. Biesen Uraemic toxins and cardiovascular disease: in vitro research versus clinical outcome studies NDT Plus, February 1, 2008; 1(1): 2 - 10. [Full Text] [PDF]

				E. N. Lavrentyev, A. M. Estes, and K. U. Malik Mechanism of High Glucose Induced Angiotensin II Production in Rat Vascular Smooth Muscle Cells Circ. Res., August 31, 2007; 101(5): 455 - 464. [Abstract] [Full Text] [PDF]