title: Nilvadipine inhibits nuclear factor-kappaB-dependent transcription in hepatic cells.
abstract: BACKGROUND
  Recent findings suggest that some dihydropyridine-type calcium channel blockers, widely used as anti-hypertensive drugs, have direct anti-atherogenic action through their antioxidant properties.
  
  
  METHODS
  We examined the effect of nilvadipine on the activity of a representative radical-sensitive transcription factor, nuclear factor kappa-B (NF-kappaB), in the human hepatocyte cell line HuH7 in vitro.
  
  
  RESULTS
  Nilvadipine potently inhibited NF-kappaB-dependent transcription in a dose- and time-dependent manner, with a minimal effective concentration of 50 nmol/l. The effect was specific because no similar effects were found in the prototype dihydropyridine nifedipine. Electromobility shift assay showed reduced protein binding to the NF-kappaB-consensus sequence in nilvadipine-treated cells. Nilvadipine also reduced the expression of fibrinogen and plasminogen activator inhibitor-1 (PAI-1).
  
  
  CONCLUSIONS
  Since NF-kappaB-mediated gene products, such as fibrinogen and PAI-1, are known to facilitate hypercoagulation, thrombosis and vascular events, we suggest that nilvadipine has a direct beneficial effect separate from its anti-hypertensive properties by inhibiting NF-kappaB-dependent gene expression and eventually inhibiting atherosclerosis.
authors.affiliation: Department of Clinical Pathophysiology, Nagoya University Graduate School of Medicine and Hospital, Nagoya 466-8550, Japan. iwasaki@med.kochi-u.ac.jp
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Iwasaki
authors.forename: Masato
authors.initials: M
authors.lastname: Asai
authors.forename: Masanori
authors.initials: M
authors.lastname: Yoshida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nigawara
authors.forename: Machiko
authors.initials: M
authors.lastname: Kambayashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oiso
authors.forename: Nobuo
authors.initials: N
authors.lastname: Nakashima
mesh_terms: D001161:Arteriosclerosis / Q000188:drug therapy; D001483:Base Sequence; D004586:Electrophoresis / Q000379:methods; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D013997:Time Factors; D051996:Transcription Factor RelA; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D016328:NF-kappa B; D017395:Plasminogen Activator Inhibitor 1; D051996:Transcription Factor RelA; C035100:nilvadipine; D005340:Fibrinogen; D009543:Nifedipine