title: Adventitial Tertiary Lymphoid Organs as Potential Source of MicroRNA Biomarkers for Abdominal Aortic Aneurysm.
abstract: Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with marked changes in the cellular composition of the aortic wall. This study aims to identify microRNA (miRNA) expression in aneurysmal inflammatory cells isolated by laser microdissection from human tissue samples. The distribution of inflammatory cells (neutrophils, B and T lymphocytes, mast cells) was evaluated in human AAA biopsies. We observed in half of the samples that adventitial tertiary lymphoid organs (ATLOs) with a thickness from 0.5 to 2 mm were located exclusively in the adventitia. Out of the 850 miRNA that were screened by microarray in isolated ATLOs (n = 2), 164 miRNAs were detected in ATLOs. The three miRNAs (miR-15a-3p, miR-30a-5p and miR-489-3p) with the highest expression levels were chosen and their expression quantified by RT-PCR in isolated ATLOs (n = 4), M1 (n = 2) and M2 macrophages (n = 2) and entire aneurysmal biopsies (n = 3). Except for the miR-30a-5p, a similar modulation was found in ATLOs and the two subtypes of macrophages. The modulated miRNAs were then evaluated in the plasma of AAA patients for their potential as AAA biomarkers. Our data emphasize the potential of miR-15a-3p and miR-30a-5p as biomarkers of AAA but also as triggers of ATLO evolution. Further investigations will be required to evaluate their targets in order to better understand AAA pathophysiology.
authors.affiliation: National Institute of Health and Medical Research (INSERM) U1167, Lille Pasteur Institute, Lille North of France University, F-59000 Lille, France. rafaelle.spear@pasteur-lille.fr.
authors.forename: Rafaelle
authors.initials: R
authors.lastname: Spear
authors.affiliation: National Institute of Health and Medical Research (INSERM) U1167, Lille Pasteur Institute, Lille North of France University, F-59000 Lille, France. ludovic.boytard@laposte.net.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Boytard
authors.affiliation: INSERM U1019, National Center of Scientific Research (CNRS) Join Research Unit (UMR) 8204, Lille Pasteur Institute, Lille North of France University, F-59000 Lille, France. renaudblervaque@hotmail.com.
authors.forename: Renaud
authors.initials: R
authors.lastname: Blervaque
authors.affiliation: National Institute of Health and Medical Research (INSERM) U1167, Lille Pasteur Institute, Lille North of France University, F-59000 Lille, France. maggy.chwastyniak@pasteur-lille.fr.
authors.forename: Maggy
authors.initials: M
authors.lastname: Chwastyniak
authors.affiliation: INSERM U1019, National Center of Scientific Research (CNRS) Join Research Unit (UMR) 8204, Lille Pasteur Institute, Lille North of France University, F-59000 Lille, France. david.hot@pasteur-lille.fr.
authors.forename: David
authors.initials: D
authors.lastname: Hot
authors.affiliation: INSERM U1011, Lille Pasteur Institute, Lille North of France University, F-59000 Lille, France. jonathan.vanhoutte@pasteur-lille.fr.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Vanhoutte
authors.affiliation: INSERM U1011, Lille Pasteur Institute, Lille North of France University, F-59000 Lille, France. bart.staels@pasteur-lille.fr.
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.affiliation: INSERM U1019, National Center of Scientific Research (CNRS) Join Research Unit (UMR) 8204, Lille Pasteur Institute, Lille North of France University, F-59000 Lille, France. yves.lemoine@pasteur-lille.fr.
authors.forename: Yves
authors.initials: Y
authors.lastname: Lemoine
authors.affiliation: National Institute of Health and Medical Research (INSERM) U1167, Lille Pasteur Institute, Lille North of France University, F-59000 Lille, France. nicolas.lamblin@chru-lille.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lamblin
authors.affiliation: Lille Regional University Hospital, F-59037 Lille, France. francois-rene.pruvot@chru-lille.fr.
authors.forename: François-René
authors.initials: FR
authors.lastname: Pruvot
authors.affiliation: INSERM U1008, Lille North of France University, Lille Regional University Hospital, F-59000 Lille, France. stephan.haulon@chru-lille.fr.
authors.forename: Stephan
authors.initials: S
authors.lastname: Haulon
authors.affiliation: National Institute of Health and Medical Research (INSERM) U1167, Lille Pasteur Institute, Lille North of France University, F-59000 Lille, France. philippe.amouyel@pasteur-lille.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Amouyel
authors.affiliation: National Institute of Health and Medical Research (INSERM) U1167, Lille Pasteur Institute, Lille North of France University, F-59000 Lille, France. florence.pinet@pasteur-lille.fr.
authors.forename: Florence
authors.initials: F
authors.lastname: Pinet
mesh_terms: D063194:Adventitia / Q000378:metabolism* / Q000503:physiopathology; D000368:Aged; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000150:complications / Q000235:genetics / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D003327:Coronary Disease / Q000209:etiology; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000302:isolation & purification / Q000378:metabolism*; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000235:genetics / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: abdominal aortic aneurysm; adventitial tertiary lymphoid organs; laser microdissection; microRNA; quantitative RT-PCR