Mass-spectrometric identification of a novel angiotensin peptide in human plasma
Standard
Mass-spectrometric identification of a novel angiotensin peptide in human plasma. / 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.
in: ARTERIOSCL THROM VAS, Jahrgang 27, Nr. 2, 02.2007, S. 297-302.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Mass-spectrometric identification of a novel angiotensin peptide in human plasma
AU - Jankowski, Vera
AU - Vanholder, Raymond
AU - van der Giet, Markus
AU - Tölle, Markus
AU - Karadogan, Sevil
AU - Gobom, Johan
AU - Furkert, Jens
AU - Oksche, Alexander
AU - Krause, Eberhard
AU - Tran, Thi Nguyet Anh
AU - Tepel, Martin
AU - Schuchardt, Mirjam
AU - Schlüter, Hartmut
AU - Wiedon, Annette
AU - Beyermann, Michael
AU - Bader, Michael
AU - Todiras, Mihail
AU - Zidek, Walter
AU - Jankowski, Joachim
PY - 2007/2
Y1 - 2007/2
N2 - 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.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.
AB - 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.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.
KW - Aged
KW - Angiotensin II
KW - Angiotensins
KW - Animals
KW - Cardiovascular Physiological Phenomena
KW - Cardiovascular System
KW - Cell Line
KW - Cells, Cultured
KW - Female
KW - Humans
KW - Kidney Failure, Chronic
KW - Male
KW - Mass Spectrometry
KW - Mice
KW - Mice, Knockout
KW - Middle Aged
KW - Rats
KW - Receptor, Angiotensin, Type 2
KW - Vasoconstriction
KW - Journal Article
U2 - 10.1161/01.ATV.0000253889.09765.5f
DO - 10.1161/01.ATV.0000253889.09765.5f
M3 - SCORING: Journal article
C2 - 17138938
VL - 27
SP - 297
EP - 302
JO - ARTERIOSCL THROM VAS
JF - ARTERIOSCL THROM VAS
SN - 1079-5642
IS - 2
ER -