title: Aorta macrophage inflammatory and epigenetic changes in a murine model of obstructive sleep apnea: Potential role of CD36.
abstract: Obstructive sleep apnea (OSA) affects 8-10% of the population, is characterized by chronic intermittent hypoxia (CIH), and causally associates with cardiovascular morbidities. In CIH-exposed mice, closely mimicking the chronicity of human OSA, increased accumulation and proliferation of pro-inflammatory metabolic M1-like macrophages highly expressing CD36, emerged in aorta. Transcriptomic and MeDIP-seq approaches identified activation of pro-atherogenic pathways involving a complex interplay of histone modifications in functionally-relevant biological pathways, such as inflammation and oxidative stress in aorta macrophages. Discontinuation of CIH did not elicit significant improvements in aorta wall macrophage phenotype. However, CIH-induced aorta changes were absent in CD36 knockout mice, Our results provide mechanistic insights showing that CIH exposures during sleep in absence of concurrent pro-atherogenic settings (i.e., genetic propensity or dietary manipulation) lead to the recruitment of CD36(+)highmacrophages to the aortic wall and trigger atherogenesis. Furthermore, long-term CIH-induced changes may not be reversible with usual OSA treatment.
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA.
authors.forename: Rene
authors.initials: R
authors.lastname: Cortese
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Gileles-Hillel
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, 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 Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Almendros
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, 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: Section of Pediatric Sleep Medicine, Department of Pediatrics, 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 Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA.
authors.forename: Zhuanghong
authors.initials: Z
authors.lastname: Qiao
authors.affiliation: Center for Research Informatics, The University of Chicago, Chicago, IL, USA.
authors.forename: Tzintzuni
authors.initials: T
authors.lastname: Garcia
authors.affiliation: Center for Research Informatics, 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 Pediatrics, 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: D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001025:Aortitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D016130:Immunophenotyping; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D020181:Sleep Apnea, Obstructive / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D018955:CD36 Antigens