TY - JOUR
T1 - Relationship Between Plasma Osteopontin and Arginine Pathway Metabolites in Patients With Overt Coronary Artery Disease
AU - Moschetta, Donato
AU - Di Minno, Matteo Nicola Dario
AU - Porro, Benedetta
AU - Perrucci, Gianluca L.
AU - Valerio, Vincenza
AU - Alfieri, Valentina
AU - Massaiu, Ilaria
AU - Orekhov, Alexander N.
AU - Di Minno, Alessandro
AU - Songia, Paola
AU - Cavalca, Viviana
AU - Myasoedova, Veronika A.
AU - Poggio, Paolo
N1 - Funding Information:
Funding. This work was supported by the Italian Ministry of Health funds (Ricerca Corrente: RC2016-BIO34-2627243 and RC2019-CA1A-2755299) and by Fondazione Gigi e Pupa Ferrari ONLUS (FPF-14).
Publisher Copyright:
© Copyright © 2020 Moschetta, Di Minno, Porro, Perrucci, Valerio, Alfieri, Massaiu, Orekhov, Di Minno, Songia, Cavalca, Myasoedova and Poggio.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/8/6
Y1 - 2020/8/6
N2 - Introduction: Osteopontin (OPN) is involved in ectopic calcification. Its circulating form is upregulated in coronary artery disease (CAD) patients. Circulating OPN levels positively correlate with oxidative stress, one of the major triggers of endothelial dysfunction. Endothelial dysfunction is, in turn, associated with reduced nitric oxide (NO) bioavailability due to the impaired arginine pathway. The aim of this study was to better understand the correlations between OPN, oxidative stress markers, and the arginine pathway metabolites. Methods and Results: ELISA and mass spectrometry techniques have been used to evaluate circulating OPN and arginine pathway/oxidative stress metabolites, respectively, in twenty-five control subjects and thirty-three patients with overt atherosclerosis. OPN positively correlates with 2,3-dinor-8isoPGF2a levels (p = 0.02), ornithine (p = 0.01), ADMA (p = 0.001), SDMA (p = 0.03), and citrulline (p = 0.008) levels only in CAD patients. In addition, citrulline positively correlated with ADMA (p = 0.02) levels, possibly as result of other sources of citrulline biosynthetic pathways. Conclusion: The association between OPN and impaired arginine/NO pathway could play a role in the inhibition of endothelial NO synthase (eNOS) and/or in the arginase activation in the context of CAD patients. However, further studies are needed to verify the cause-effect relationship between OPN, oxidative stress, and arginine/NO pathway dysregulation.
AB - Introduction: Osteopontin (OPN) is involved in ectopic calcification. Its circulating form is upregulated in coronary artery disease (CAD) patients. Circulating OPN levels positively correlate with oxidative stress, one of the major triggers of endothelial dysfunction. Endothelial dysfunction is, in turn, associated with reduced nitric oxide (NO) bioavailability due to the impaired arginine pathway. The aim of this study was to better understand the correlations between OPN, oxidative stress markers, and the arginine pathway metabolites. Methods and Results: ELISA and mass spectrometry techniques have been used to evaluate circulating OPN and arginine pathway/oxidative stress metabolites, respectively, in twenty-five control subjects and thirty-three patients with overt atherosclerosis. OPN positively correlates with 2,3-dinor-8isoPGF2a levels (p = 0.02), ornithine (p = 0.01), ADMA (p = 0.001), SDMA (p = 0.03), and citrulline (p = 0.008) levels only in CAD patients. In addition, citrulline positively correlated with ADMA (p = 0.02) levels, possibly as result of other sources of citrulline biosynthetic pathways. Conclusion: The association between OPN and impaired arginine/NO pathway could play a role in the inhibition of endothelial NO synthase (eNOS) and/or in the arginase activation in the context of CAD patients. However, further studies are needed to verify the cause-effect relationship between OPN, oxidative stress, and arginine/NO pathway dysregulation.
KW - atherosclerosis
KW - citrulline
KW - endothelial dysfunction
KW - nitric oxide
KW - OPN
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U2 - 10.3389/fphys.2020.00982
DO - 10.3389/fphys.2020.00982
M3 - Article
AN - SCOPUS:85089844759
VL - 11
JO - Frontiers in Physiology
JF - Frontiers in Physiology
SN - 1664-042X
M1 - 982
ER -