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

Item Type:Article
Title:Mass-spectrometric identification of a novel angiotensin peptide in human plasma
Creators Name:Jankowski, V. and Vanholder, R. and van der Giet, M. and Toelle, M. and Karadogan, S. and Gobom, J. and Furkert, J. and Oksche, A. and Krause, E. and Tran, T.N. and Tepel, M. and Schuchardt, M. and Schlueter, H. and Wiedon, A. and Beyermann, M. and Bader, M. and Todiras, M. and Zidek, W. and Jankowski, J.
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 Ala(1) instead of Asp(1). Des[Asp(1)]-[Ala(1)]-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 Asp(1). 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. CONCLUSIONS: 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.
Keywords:Mass-Spectrometry, Vasoconstriction, Angiotensin-Peptide, Human Plasma, Animals, Mice, Rats
Source:Arteriosclerosis Thrombosis and Vascular Biology
Publisher:American Heart Association
Page Range:297-302
Date:February 2007
Official Publication:https://doi.org/10.1161/01.ATV.0000253889.09765.5f
PubMed:View item in PubMed

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