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.
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: Brian Lawlor; Ricardo Segurado; Sean Kennelly; Marcel G M Olde Rikkert; Robert Howard; Florence Pasquier; Anne Börjesson-Hanson; Magda Tsolaki; Ugo Lucca; D William Molloy; Robert Coen; Matthias W Riepe; János Kálmán; Rose Anne Kenny; Fiona Cregg; Sarah O'Dwyer; Cathal Walsh; Jessica Adams; Rita Banzi; Laetitia Breuilh; Leslie Daly; Suzanne Hendrix; Paul Aisen; Siobhan Gaynor; Ali Sheikhi; Diana G Taekema; Frans R Verhey; Raffaello Nemni; Flavio Nobili; Massimo Franceschi; Giovanni Frisoni; Orazio Zanetti; Anastasia Konsta; Orologas Anastasios; Styliani Nenopoulou; Fani Tsolaki-Tagaraki; Magdolna Pakaski; Olivier Dereeper; Vincent de la Sayette; Olivier Sénéchal; Isabelle Lavenu; Agnès Devendeville; Gauthier Calais; Fiona Crawford; Michael Mullan Journal: PLoS Med Date: 2018-09-24 Impact factor: 11.069