title: Extracellular microvesicle microRNAs in children with sickle cell anaemia with divergent clinical phenotypes.
abstract: Sickle cell anaemia (SCA) is the most frequent genetic haemoglobinopathy, which exhibits a highly variable clinical course characterized by hyper-coagulable and pro-inflammatory states, as well as endothelial dysfunction. Extracellular microvesicles are released into biological fluids and play a role in modifying the functional phenotype of target cells. We hypothesized that potential differences in plasma-derived extracellular microvesicles (EV) function and cargo from SCA patients may underlie divergent clinical trajectories. Plasma EV from SCA patients with mild, intermediate and severe clinical disease course were isolated, and primary endothelial cell cultures were exposed. Endothelial cell activation, monocyte adhesion, barrier disruption and exosome cargo (microRNA microarrays) were assessed. EV disrupted the endothelial barrier and induced expression of adhesion molecules and monocyte adhesion in a SCA severity-dependent manner compared to healthy children. Microarray approaches identified a restricted signature of exosomal microRNAs that readily distinguished severe from mild SCA, as well as from healthy children. The microRNA candidates were further validated using quantitative real time polymerase chain reaction assays, and revealed putative gene targets. Circulating exosomal microRNAs may play important roles in predicting the clinical course of SCA, and in delineation of individually tailored, mechanistically-based clinical treatment approaches of SCA patients in the near future.
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Paediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA.
authors.forename: Abdelnaby
authors.initials: A
authors.lastname: Khalyfa
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Paediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA.
authors.forename: Ahamed A
authors.initials: AA
authors.lastname: Khalyfa
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Paediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA.
authors.forename: Mahzad
authors.initials: M
authors.lastname: Akbarpour
authors.affiliation: UMR Inserm U1134, French West Indies University, Pointe-à-Pitre, Guadeloupe, France.|Laboratoire d'Excellence du Globule Rouge (LABEX GR-Ex), PRES Sorbonne, Paris, France.|Institut Universitaire de France (IUF), Paris, France.|Laboratory LIBM, Team "Vascular Biology and Red Blood Cell", University of Lyon 1, Lyon, France.
authors.forename: Phillippe
authors.initials: P
authors.lastname: Connes
authors.affiliation: UMR Inserm U1134, French West Indies University, Pointe-à-Pitre, Guadeloupe, France.|Laboratoire d'Excellence du Globule Rouge (LABEX GR-Ex), PRES Sorbonne, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Romana
authors.affiliation: Pediatric Hematology-Oncology, Department of Paediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Lapping-Carr
authors.affiliation: Center for Research Informatics, Sciences Division, The University of Chicago, Chicago, IL, USA.
authors.forename: Chunling
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Center for Research Informatics, Sciences Division, The University of Chicago, Chicago, IL, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Andrade
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Paediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA.
authors.forename: David
authors.initials: D
authors.lastname: Gozal
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000175:diagnosis / Q000473:pathology*; D000818:Animals; D002460:Cell Line; D055252:Cell-Derived Microparticles / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D055354:Exosomes / Q000235:genetics / Q000473:pathology*; D005110:Extracellular Space / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000032:analysis* / Q000302:isolation & purification; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011379:Prognosis; D012720:Severity of Illness Index
chemical_list: D035683:MicroRNAs
keywords: endothelial function; exosomes; sickle cell anaemia