title: Increased C-C chemokine receptor 2 gene expression in monocytes of severe obstructive sleep apnea patients and under intermittent hypoxia.
abstract: BACKGROUND
  Obstructive sleep apnea (OSA) is known to be a risk factor of coronary artery disease. The chemotaxis and adhesion of monocytes to the endothelium in the early atherosclerosis is important. This study aimed to investigate the effect of intermittent hypoxia, the hallmark of OSA, on the chemotaxis and adhesion of monocytes.
  
  
  METHODS
  Peripheral blood was sampled from 54 adults enrolled for suspected OSA. RNA was prepared from the isolated monocytes for the analysis of C-C chemokine receptor 2 (CCR2). The effect of intermittent hypoxia on the regulation and function of CCR2 was investigated on THP-1 monocytic cells and monocytes. The mRNA and protein expression levels were investigated by RT/real-time PCR and western blot analysis, respectively. Transwell filter migration assay and cell adhesion assay were performed to study the chemotaxis and adhesion of monocytes.
  
  
  RESULTS
  Monocytic CCR2 gene expression was found to be increased in severe OSA patients and higher levels were detected after sleep. Intermittent hypoxia increased the CCR2 expression in THP-1 monocytic cells even in the presence of TNF-α and CRP. Intermittent hypoxia also promoted the MCP-1-mediated chemotaxis and adhesion of monocytes to endothelial cells. Furthermore, inhibitor for p42/44 MAPK or p38 MAPK suppressed the activation of monocytic CCR2 expression by intermittent hypoxia.
  
  
  CONCLUSIONS
  This is the first study to demonstrate the increase of CCR2 gene expression in monocytes of severe OSA patients. Monocytic CCR2 gene expression can be induced under intermittent hypoxia which contributes to the chemotaxis and adhesion of monocytes.
authors.affiliation: Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Sleep Center, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Li-Pang
authors.initials: LP
authors.lastname: Chuang
authors.affiliation: Sleep Center, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Ning-Hung
authors.initials: NH
authors.lastname: Chen
authors.affiliation: Sleep Center, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Lin
authors.affiliation: Department of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Ying-Ling
authors.initials: YL
authors.lastname: Chang
authors.affiliation: Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Hsiang-Ruei
authors.initials: HR
authors.lastname: Liao
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Lin
authors.affiliation: Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: I-Ju
authors.initials: IJ
authors.lastname: Chao
authors.affiliation: Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Jong-Hwei S
authors.initials: JH
authors.lastname: Pang
mesh_terms: D000328:Adult; D002448:Cell Adhesion; D015687:Cell Hypoxia; D002478:Cells, Cultured; D002633:Chemotaxis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D054390:Receptors, CCR2 / Q000235:genetics* / Q000378:metabolism*; D020181:Sleep Apnea, Obstructive / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C515334:CCR2 protein, human; D054390:Receptors, CCR2