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Increased serum homocitrulline concentrations are associated with the severity of coronary artery disease

  • Stéphane Jaisson EMAIL logo , Mohsen Kerkeni , Izabella C.R. Santos-Weiss , Faouzi Addad , Mohammed Hammami and Philippe Gillery
Published/Copyright: August 7, 2014

Abstract

Background: Carbamylation is a non-enzymatic post-translational modification of proteins that has been recently identified as a non-traditional risk factor for atherosclerosis. The aim of this study was to determine whether serum homocitrulline (HCit), a characteristic carbamylation-derived product, was related to the presence and the severity of coronary artery disease (CAD).

Methods: Forty-five control subjects and 109 patients were included in this cross-sectional study. After coronary angiography, the patients were classified as non-CAD patients (patients with normal arteries, n=33) and CAD patients (n=76). The severity of CAD was then evaluated using the Gensini scoring system. Serum total HCit concentrations were determined by LC-MS/MS.

Results: Serum HCit concentrations were significantly (p<0.001) higher in CAD patients than in control or non-CAD subjects. The receiver operating characteristic curve analysis showed an area under the curve equal to 0.908 (95% confidence interval, 0.853–0.964, p<0.001) and a threshold HCit concentration of 0.16 mmol/mol Lys for predicting the presence of CAD (78.9% sensitivity and 78.8% specificity). HCit concentrations significantly (p<0.001) increased concomitantly with the severity of CAD and were positively correlated with Gensini scores (r=0.725, p<0.001) as well as with the number of stenotic coronary arteries (p<0.001). Furthermore, in a multiple stepwise regression analysis, HCit was significantly (p<0.001) and independently associated with the presence of CAD, the Gensini score, and the number of stenotic arteries (standardized β values of 0.525, 0.722, and 0.642, respectively).

Conclusions: Our results demonstrate that serum HCit concentrations are increased during CAD and are positively associated with the severity of the disease.


Corresponding author: Dr. Stéphane Jaisson, Laboratory of Biochemistry and Molecular Biology, Faculty of Medicine, UMR CNRS/URCA no7369, 51 Rue Cognacq-Jay, 51095 Reims, France, Phone: +33-3-26-91-83-00, Fax: +33-3-26-91-80-55, E-mail:
aStéphane Jaisson and Mohsen Kerkeni participated equally in this work.

Acknowledgments

The authors thank C. Desroches and N. Leroy for technical assistance.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Financial support: This work was supported by funds from the University of Reims Champagne-Ardenne (URCA) (France), the Centre National de la Recherche Scientifique (CNRS, France) and the “Ministère Tunisien de l’Enseignement Supérieur et de la Recherche Scientifique” (LR12ES05, University of Monastir, Tunisia). I.C.R.S.W. was the recipient of a grant from the Brazilian government (CAPES).

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2014-6-19
Accepted: 2014-7-8
Published Online: 2014-8-7
Published in Print: 2015-1-1

©2015 by De Gruyter

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