Alcohol at Moderate Levels Decreases Fibrinogen Expression In Vivo and In Vitro

Abstract

Consumption of moderate amounts of alcohol has been reported to exert a cardioprotective effect in individuals. The exact mechanism by which this occurs has not been fully explored. Circulating levels of the clotting protein fibrinogen have been unequivocally established as an independent risk factor for vascular diseases. This study examined the effects of moderate levels of ethanol on the expression of fibrinogen in an animal model and in hepatoma cells. Out-bred Sprague-Dawley rats were fed 5% ethanol (v/v) in their water for 4 weeks, and circulating levels of fibrinogen were measured weekly via quantitative immunoassay. H4IIE rat hepatoma cells, which constitutively produce fibrinogen, were exposed to 10 and 20 mM ethanol, and fibrinogen production was determined. The effects of ethanol on fibrinogen messenger ribonucleic acids were determined by northern gel analyses. Our findings demonstrate that daily consumption of moderate amounts of ethanol decreases circulating levels of fibrinogen 18% to 20%. The decrease is reversible and is not gender specific. The exposure of hepatoma cells to ethanol also diminishes fibrinogen production by 20% by decreasing the transcription of fibrinogen genes. Alcohol concentration of 10 to 20 mM did not affect hepatoma cell viability or doubling time. The findings indicate that one likely positive benefit of moderate ethanol consumption is to diminish the production of fibrinogen, which reduces the potential risk exerted by this protein. The site of action of ethanol is, at least in part, exerted at the level of gene transcription.