title: Niacin affects cell adhesion molecules and plasminogen activator inhibitor-1 in HepG2 cells.
abstract: BACKGROUND
  Beyond lipid-modifying actions, niacin lowers the risk of atherothrombotic events by lowering prothrombotic factors like fibrinogen. Plasminogen activator inhibitor type 1 (PAI-1) is a potential factor for atherogenesis and thrombosis, increased in acute myocardial infarctions and restenosis after angioplasty. Cell adhesion molecules (CAM) mediate adhesion, recruitment and migration of white blood cells through vascular surfaces, an essential process in atherogenesis. ICAM-1 is a significant predictor of future coronary events. Whether niacin affects ICAM-1 expression is unknown. We studied the effects of niacin on PAI-1 and CAM using HepG2 cells.
  
  
  METHODS
  HepG2 cells were cultured in DMEM until 90% confluent. After serum starvation, cells were exposed to DME/F12 containing niacin. Transforming growth factor-beta (TGF-beta) was added directly to cell media. Cell lysate and conditioned media were collected for measurement of PAI-1 by ELISA. For measurement of ICAM, cells were treated with tumor necrosis factor-alpha (TNF-alpha) instead. The effect of niacin on mRNA expression of ICAM-1 was studied using RT-PCR.
  
  
  RESULTS
  Niacin reduced the TGF-beta-induced rise by 30% to 55% (p=0.002). The differences in degree of PAI-1 reduction, between different niacin concentrations, were not statistically significant. Niacin reduced TNF-alpha-induced rise in ICAM-1 levels by 66% to 89% (p<0.0001), but did not significantly affect TNF-alpha-induced rise in PECAM-1. Semiquantitative RT-PCR analysis showed that reduced TNF-alpha-induced rise in ICAM-1 mRNA expression significantly by 17% (p=0.001).
  
  
  CONCLUSIONS
  Treatment with niacin suppressed PAI-1 and ICAM-1 levels in HepG2 cells. Further studies to understand the mechanistic pathways of this suppression, could further explain benefits of niacin in prevention of atherosclerotic disease, and offer therapeutic avenues against the rising burden of atherothrombotic disease.
authors.affiliation: Department of Medicine, Diabetes Centre, Alexandra Hospital, 378 Alexandra Rd., Singapore 159964, Singapore. tavintharan_subramaniam@alexhosp.com.sg
authors.forename: S
authors.initials: S
authors.lastname: Tavintharan
authors.forename: M
authors.initials: M
authors.lastname: Sivakumar
authors.forename: S C
authors.initials: SC
authors.lastname: Lim
authors.forename: C F
authors.initials: CF
authors.lastname: Sum
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D009525:Niacin / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D015815:Cell Adhesion Molecules; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D009525:Niacin