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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/19848

Title: Endothelium-enriched microRNAs as diagnostic biomarkers for cardiac allograft vasculopathy
Authors: Singh, Neha
Heggermont, Ward
Fieuws, Steffen
Vanhaecke, Johan
Van Cleemput, Johan
De Geest, Bart
Issue Date: 2015
Citation: JOURNAL OF HEART AND LUNG TRANSPLANTATION, 34 (11), p. 1376-1384
Abstract: BACKGROUND: Cardiac allograft vasculopathy (CAV) is a limiting factor for the long-term survival of heart transplant recipients. Clinical decisions and care may be improved by the development of prediction models based on circulating biomarkers. The endothelium may play a central pathogenetic role in the development of CAV. We evaluated the hypothesis that endothelium-enriched microRNAs (miRNAs) discriminate between patients with and without CAV. METHODS: This cross-sectional study recruited 52 patients undergoing coronary angiography between 5 and 15 years after heart transplantation. Circulating levels of endothelium-enriched miRNAs (miR-21-5p, miR-92a-3p, miR-92a-1-5p, miR-126-3p, and miR-126-5p) were quantified by real-time reverse transcription polymerase chain reaction. The discriminative ability of logistic regression models was evaluated using the concordance (C) statistic. RESULTS: Median plasma levels of miR-210-5p, miR-92a-3p, miR- I26-3p, and miR-126-5p were 1.82-fold (p = not significant), 1.87-fold (p < 0.05), 1.94-fold (p = 0.074), and 1.59-fold (p = 0.060) higher in patients with CAV than in patients without CAV. Recipient age (C statistic = 0.689; 95% confidence interval [CI], 0.537-0.842), and levels of serum creatinine (C statistic = 0.703; 95% Cl, 0.552-0.854), miR-92a-3p (C statistic = 0.682; 95% CI, 0.533-0.831), and miR-126-5p (C statistic = 0.655; 95% CI, 0.502-0.807) predicted CAV status in univariable models. In multivariable logistic regression models with recipient age and creatinine as covariates, miR-I26-5p (chi-square = 4.371, p = 0.037), miR-92a3p (chi-square = 6.0l, p = 0.014), and the combination of miR-126-5p and miR-92a-3p (chi-square = 8.162, p = 0.017) added significant information. The model with age, creatinine, miR- I26-5p, and miR92a-3p as covariables conferred good discrimination between patients without and with CAV (C statistic = 0.800; 95% CI, 0.674-0.926). CONCLUSIONS: Endothelium-enriched miRNAs have diagnostic ability for CAV beyond clinical predictors. (C) 2015 International Society for Heart and Lung Transplantation. All rights reserved.
Notes: [Singh, Neha; Heggermont, Ward; De Geest, Bart] Catholic Univ, Ctr Mol & Vasc Biol, B-3000 Leuven, Belgium. [Heggermont, Ward; Vanhaecke, Johan; Van Cleemput, Johan] Catholic Univ, Dept Cardiovasc Sci, Cardiol, B-3000 Leuven, Belgium. [Fieuws, Steffen] Univ Leuven, Interuniv Inst Biostat & Stat Bioinformat, Leuven, Belgium. [Fieuws, Steffen] Univ Hasselt, Leuven, Belgium.
URI: http://hdl.handle.net/1942/19848
DOI: 10.1016/j.healun.2015.06.008
ISI #: 000364273400003
ISSN: 1053-2498
Category: A1
Type: Journal Contribution
Validation: ecoom, 2016
Appears in Collections: Research publications

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