Pro‐atherogenic effects of probucol may be mediated through alterations in the coagulation system in apo E‐KO mice

Abstract

We have previously shown that probucol paradoxically increases atherogenesis in apo E‐KO mice, while dietary phytosterol significantly reduce the disease in this animal model. Male apo E‐KO mice were fed with an atherogenic diet containing 9% (w/w) fat and 0.2% (w/w) cholesterol in the presence of either 2% (w/w) dietary phytosterol mixture (phytosterol‐treated group, n=8), or 1% (w/w) probucol (probucol‐treated group, n=8) or nothing (control group, n=8) for 18 weeks. Plasma total cholesterol levels were significantly decreased in both treated groups as compared to controls. Aortic atherosclerotic lesion size was significantly lower in the phytosterol‐treated and significantly higher in the probucol‐treated mice as compared to controls. Plasma and aortic PAI‐1 levels were significantly higher in the probucol‐treated animals as compared to controls, while these values were comparable between the phytosterol‐treated and control mice. Both DNA microarray and RT‐PCR tests showed a significant increase in the expression of F13a1 in the liver of probucol treated mice as compared to controls. These observations suggest that pro‐atherogenic effects of probucol maybe mediated through alterations in the coagulation system in this animal model.