title: Intermittent Hypoxia Alters Gene Expression in Peripheral Blood Mononuclear Cells of Healthy Volunteers.
abstract: Obstructive sleep apnea is associated with high cardiovascular morbidity and mortality. Intermittent hypoxia of obstructive sleep apnea is implicated in the development and progression of insulin resistance and atherosclerosis, which have been attributed to systemic inflammation. Intermittent hypoxia leads to pro-inflammatory gene up-regulation in cell culture, but the effects of intermittent hypoxia on gene expression in humans have not been elucidated. A cross-over study was performed exposing eight healthy men to intermittent hypoxia or control conditions for five hours with peripheral blood mononuclear cell isolation before and after exposures. Total RNA was isolated followed by gene microarrays and confirmatory real time reverse transcriptase PCR. Intermittent hypoxia led to greater than two fold up-regulation of the pro-inflammatory gene toll receptor 2 (TLR2), which was not increased in the control exposure. We hypothesize that up-regulation of TLR2 by intermittent hypoxia may lead to systemic inflammation, insulin resistance and atherosclerosis in patients with obstructive sleep apnea.
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Vsevolod Y
authors.initials: VY
authors.lastname: Polotsky
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Shannon
authors.initials: S
authors.lastname: Bevans-Fonti
authors.affiliation: Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Dmitry N
authors.initials: DN
authors.lastname: Grigoryev
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.|Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Naresh M
authors.initials: NM
authors.lastname: Punjabi
mesh_terms: D000293:Adolescent; D000328:Adult; D050197:Atherosclerosis / Q000235:genetics; D018592:Cross-Over Studies; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000097:blood* / Q000503:physiopathology; D007249:Inflammation / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000502:physiology*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012016:Reference Values; D020181:Sleep Apnea, Obstructive / Q000097:blood / Q000503:physiopathology; D051195:Toll-Like Receptor 2 / Q000235:genetics; D015854:Up-Regulation
chemical_list: C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2