Hypercholesterolaemia provokes reactive oxygen species (ROS) increase and is a major risk factor for cardiovascular disease (CVD) development. We previously showed that circulating miR-33a/b expression levels were up-regulated in children with familial hypercholesterolaemia (FH). miR-33a/b control cholesterol homoeostasis and recently miR-33b has been demonstrated to directly target the transcription factor zinc finger E-box-binding homeobox 1 (ZEB1). The latter acts in a negative feedback loop with the miR-200 family. Our previous studies showed that the ROS-dependent miR-200c up-regulation induces endothelial dysfunction and provokes a ZEB1-dependent apoptosis and senescence. In the present study, we aimed to verify whether circulating miR-200c was induced in FH children, and whether a correlation existed with miR-33a/b. Total RNA was extracted from plasma of 28 FH children and 25 age-matched healthy subjects (HS) and miR-200c levels were measured. We found that miR-200c was up-regulated in FH compared with HS (4.00 ± 0.48-fold increase, P<0.05) and exhibited a positive correlation with miR-33a/b. miR-200c did not correlate with plasma lipids, but correlated with C-reactive protein (CRP) plasma levels and glycaemia (GLI). Ordinary least squares (OLS) regression analysis revealed that miR-200c was significantly affected by GLI and by miR-33a (P<0.01; P<0.001 respectively). Moreover, we found that miR-33 overexpression, in different cell lines, decreased ZEB1 expression and up-regulated both the intracellular and the extracellular miR-200c expression levels. In conclusion, circulating miR-200c is up-regulated in FH, probably due to oxidative stress and inflammation and via a miR-33a/b-ZEB1-dependent mechanism. The present study could provide the first evidence to point to the use of miR-33a/b and miR-200c, as early biomarkers of CVD, in paediatric FH.
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A flurogold labeled-retina flatmount (front) representing surviving retinal ganglion cells, and the chemical structure of trimetazidine (background). In Clinical Science volume 131, issue 18, Wan et al. report that trimetazidine protects retinal ganglion cells against acute glaucoma via the Nrf2/Ho-1 pathway and propose it as a novel therapeutic agent; for details, see pages 2363-2375.
Research Article|
September 08 2017
Circulating miR-200c is up-regulated in paediatric patients with familial hypercholesterolaemia and correlates with miR-33a/b levels: implication of a ZEB1-dependent mechanism
Marco D’Agostino;
Marco D’Agostino
*
1Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, Rome 00161, Italy
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Francesco Martino;
Francesco Martino
*
2Center of Clinic Lipid Research, Paediatric Cardiology, Department of Paediatrics, Sapienza University of Rome, Viale Regina Elena 324, Rome 00161, Italy
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Sara Sileno;
Sara Sileno
3Istituto Dermopatico dell’Immacolata-IRCCS, FLMM, Vascular Pathology Laboratory, Via dei Monti di Creta 104, Rome 00167, Italy
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Francesco Barillà;
Francesco Barillà
4Department of Heart and Large Vessels “A. Reale”, Sapienza University of Rome, Viale del Policlinico 155, Rome 00161, Italy
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Sara Beji;
Sara Beji
3Istituto Dermopatico dell’Immacolata-IRCCS, FLMM, Vascular Pathology Laboratory, Via dei Monti di Creta 104, Rome 00167, Italy
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Lorenza Marchetti;
Lorenza Marchetti
3Istituto Dermopatico dell’Immacolata-IRCCS, FLMM, Vascular Pathology Laboratory, Via dei Monti di Creta 104, Rome 00167, Italy
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Fabio Maria Gangi;
Fabio Maria Gangi
3Istituto Dermopatico dell’Immacolata-IRCCS, FLMM, Vascular Pathology Laboratory, Via dei Monti di Creta 104, Rome 00167, Italy
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Luca Persico;
Luca Persico
5Department of Economics and Business Studies, University of Genoa, Via F. Vivaldi 5, Genoa 16126, Italy
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Mario Picozza;
Mario Picozza
3Istituto Dermopatico dell’Immacolata-IRCCS, FLMM, Vascular Pathology Laboratory, Via dei Monti di Creta 104, Rome 00167, Italy
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Anna Montali;
Anna Montali
6Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, Rome 00161, Italy
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Eliana Martino;
Eliana Martino
2Center of Clinic Lipid Research, Paediatric Cardiology, Department of Paediatrics, Sapienza University of Rome, Viale Regina Elena 324, Rome 00161, Italy
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Cristina Zanoni;
Cristina Zanoni
2Center of Clinic Lipid Research, Paediatric Cardiology, Department of Paediatrics, Sapienza University of Rome, Viale Regina Elena 324, Rome 00161, Italy
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Daniele Avitabile;
Daniele Avitabile
7IDI-Farmaceutici Srl, Marketing, Sales, BD, Via dei Castelli Romani 83/85, Pomezia 00071, Italy
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Sandro Parrotto;
Sandro Parrotto
8I Clinica Medica, Sapienza University of Rome, Via del Policlinico 155, Rome 00161, Italy
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Maurizio Colognesi Capogrossi;
Maurizio Colognesi Capogrossi
3Istituto Dermopatico dell’Immacolata-IRCCS, FLMM, Vascular Pathology Laboratory, Via dei Monti di Creta 104, Rome 00167, Italy
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Alessandra Magenta
3Istituto Dermopatico dell’Immacolata-IRCCS, FLMM, Vascular Pathology Laboratory, Via dei Monti di Creta 104, Rome 00167, Italy
Correspondence: Alessandra Magenta (ale.magenta@gmail.com)
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Publisher: Portland Press Ltd
Received:
June 09 2017
Revision Received:
August 04 2017
Accepted:
August 13 2017
Accepted Manuscript online:
August 15 2017
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2017
Clin Sci (Lond) (2017) 131 (18): 2397–2408.
Article history
Received:
June 09 2017
Revision Received:
August 04 2017
Accepted:
August 13 2017
Accepted Manuscript online:
August 15 2017
Citation
Marco D’Agostino, Francesco Martino, Sara Sileno, Francesco Barillà, Sara Beji, Lorenza Marchetti, Fabio Maria Gangi, Luca Persico, Mario Picozza, Anna Montali, Eliana Martino, Cristina Zanoni, Daniele Avitabile, Sandro Parrotto, Maurizio Colognesi Capogrossi, Alessandra Magenta; Circulating miR-200c is up-regulated in paediatric patients with familial hypercholesterolaemia and correlates with miR-33a/b levels: implication of a ZEB1-dependent mechanism. Clin Sci (Lond) 15 September 2017; 131 (18): 2397–2408. doi: https://doi.org/10.1042/CS20171121
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