title: Attenuated macrophage cholesterol efflux function in patients with obstructive sleep apnea-hypopnea syndrome.
abstract: BACKGROUND
  Obstructive sleep apnea-hypopnea syndrome (OSAHS) is associated with premature atherosclerosis. However, the associated mechanism remains unknown. This study investigates the expression of adenosine triphosphate (ATP)-binding cassette transporter protein A1 (ABCA1) and cellular cholesterol efflux in cultured macrophages from OSAHS patients.
  
  
  METHODS
  Of the 18 subjects enrolled in this study, six subjects with apnea-hypopnea index (AHI) <5 were placed into the control group, and 12 subjects with AHI ≥5 were placed into the OSAHS group. Peripheral blood mononuclear cells (PBMCs) from each subject were isolated, purified, cultured, and differentiated into macrophages in vitro. ABCA1 mRNA and protein expression were evaluated by reverse transcription PCR and Western Blot, respectively. Both ABCA1-mediated and autologous serum induced cholesterol efflux were measured by isotopic cholesterol efflux assays.
  
  
  RESULTS
  The levels of AHI and high sensitivity C-reactive protein (hsCRP) were significantly higher in the OSAHS group than in the control group. ABCA1 mRNA and protein expressions in PBMCs-derived macrophages were significantly reduced in patients with OSAHS compared to that in controls (p < 0.05). Both ABCA1-mediated and autologous serum-induced cholesterol efflux were significantly lower in the OSAHS group than that in the control group (p = 0.033 and p = 0.01, respectively). Pearson's correlation analysis revealed a negative correlation between AHI and the mRNA (r = -0.7726, p = 0.0007) and protein (r = -0.8112, p = 0.0044) expression of ABCA1, a positive correlation between ABCA1-mediated cholesterol efflux and the minimum oxygen saturation (r = 0.7954, p < 0.0001), and a negative correlation between AHI and autologous serum induced cholesterol efflux (r = -0.7756, p = 0.0002).
  
  
  CONCLUSIONS
  ABCA1 expression and cellular cholesterol efflux in macrophages were significantly decreased in OSAHS patients, which closely correlated with the severity of disease. Our findings provide meaningful insights into the mechanism of atherogenesis in OSAHS patients.
authors.affiliation: Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
authors.forename: Rui-Yi
authors.initials: RY
authors.lastname: Xu
authors.forename: Rong
authors.initials: R
authors.lastname: Huang
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiao
authors.forename: Lian-Feng
authors.initials: LF
authors.lastname: Chen
authors.forename: Xue
authors.initials: X
authors.lastname: Lin
authors.forename: Quan
authors.initials: Q
authors.lastname: Fang
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Yan
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics*; D000328:Adult; D050197:Atherosclerosis / Q000235:genetics* / Q000503:physiopathology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D020181:Sleep Apnea, Obstructive / Q000235:genetics* / Q000503:physiopathology*; D013223:Statistics as Topic
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D012333:RNA, Messenger; D002784:Cholesterol