title: Circulating miR-33a and miR-33b are up-regulated in familial hypercholesterolaemia in paediatric age.
abstract: Hypercholesterolaemia is one of the major causes of CVD (cardiovascular disease). It is associated with enhanced oxidative stress, leading to increased lipid peroxidation which in turn determines endothelial dysfunction and susceptibility to coronary vasoconstriction and atherosclerosis. Different miRNAs are involved in the pathogenesis of CVD and play an important role in inflammatory process control, therefore, together with atherogenic factors, they can stimulate atherosclerotic degeneration of the vessel walls of arteries. miR-33a and miR-33b play a pivotal role in a variety of biological processes including cholesterol homoeostasis, HDL (high-density lipoprotein)-cholesterol formation, fatty acid oxidation and insulin signalling. Our study aimed to determine whether circulating miR-33a and miR-33b expression was altered in familial hypercholesterolaemic children. Total RNA was extracted from plasma, and miR-33a and miR-33b were measured by quantitative real-time PCR. We found that miR-33a and miR-33b were significantly up-regulated in the plasma of 28 hypercholesterolaemic children compared with 25 healthy subjects (4.49±0.27-fold increase, P<0.001, and 3.21±0.39-fold increase, P<0.05 respectively), and for both miRNAs, a positive correlation with total cholesterol, LDL (low-density lipoprotein)-cholesterol, LDL-cholesterol/HDL-cholesterol ratio, apolipoprotein B, CRP (C-reactive protein) and glycaemia was found. OLS (ordinary least squares) regression analysis revealed that miR-33a was significantly affected by the presence of FH (familial hypercholesterolaemia), glycaemia and CRP (P<0.001, P<0.05 and P<0.05 respectively). The same analysis showed that miR-33b was significantly related to FH and CRP (P<0.05 and P<0.05 respectively). Although it is only explorative, the present study could be the first to point to the use of miR-33a and miR-33b as early biomarkers for cholesterol levels in childhood, once validated in independent larger cohorts.
authors.affiliation: Center of Clinic Lipid Research, Department of Pediatrics, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy ale.magenta@gmail.com francesco.martino30@tin.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Martino
authors.affiliation: Fondazione Luigi Maria Monti, Istituto Dermopatico dell'Immacolata-IRCCS, Vascular Pathology Laboratory, Via dei Monti di Creta 104, 00167 Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Carlomosti
authors.affiliation: Centro Cardiologico Monzino-IRCCS, Vascular Biology and Regenerative Medicine Laboratory, Via Parea 4, 20138 Milan, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Avitabile
authors.affiliation: Department of Economics and Business Studies, University of Genoa, Via F. Vivaldi 5, 16126, Genoa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Persico
authors.affiliation: Fondazione Luigi Maria Monti, Istituto Dermopatico dell'Immacolata-IRCCS, Vascular Pathology Laboratory, Via dei Monti di Creta 104, 00167 Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Picozza
authors.affiliation: Department of Cardiovascular, Respiratory, Nephrological, Anesthesiological and Geriatrical Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Barillà
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Arca
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Montali
authors.affiliation: Center of Clinic Lipid Research, Department of Pediatrics, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Eliana
authors.initials: E
authors.lastname: Martino
authors.affiliation: Center of Clinic Lipid Research, Department of Pediatrics, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Zanoni
authors.affiliation: I Clinica Medica, Sapienza University of Rome, Via del Policlinico 155, 00161 Rome, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Parrotto
authors.affiliation: Fondazione Luigi Maria Monti, Istituto Dermopatico dell'Immacolata-IRCCS, Vascular Pathology Laboratory, Via dei Monti di Creta 104, 00167 Rome, Italy ale.magenta@gmail.com francesco.martino30@tin.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Magenta
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D053299:Apolipoprotein B-100 / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D002648:Child; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005819:Genetic Markers; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D016018:Least-Squares Analysis; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D011237:Predictive Value of Tests; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: C569471:APOB protein, human; D053299:Apolipoprotein B-100; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005819:Genetic Markers; C550416:MIRN33a microRNA, human; D035683:MicroRNAs; D002097:C-Reactive Protein
keywords: cardiovascular disease; hypercholesterolaemia; lipoproteins; miR-33; miRNAs; paediatrics