Effects of ethyl-all-cis-5,8,11,14,17-icosapentaenoate (EPA-E), pravastatin and their combination on serum lipids and intimal thickening of cuff-sheathed carotid artery in rabbits

The anti-arteriosclerotic effects of ethyl all-cis-5, 8, 11, 14, 17-icosapentaenoate (EPA-E), pravastatin and their combination in cuff-treated rabbits were investigated. EPA-E at 600 mg/kg, pravastatin at 50 mg/kg or their combination was orally administered once daily for 5 weeks, and each of the animals was sheathed with a cuff on the carotid artery 2 weeks after the beginning of drug administration. EPA-E, pravastatin and their combination significantly reduced serum total cholesterol compared to the control group. EPA-E also potently reduced serum triglyceride, while pravastatin only slightly reduced it. The combination of these two agents had the most potent effect on the level of serum triglyceride. Serum phospholipids were also reduced by these treatments in a similar fashion. At the end of treatment, diffuse intimal thickening was observed in the cuff-covered region in all animals in the control group, and the intima/media area ratio in this group was 0.293 ± 0.038. Treatment with EPA-E alone tended to prevent the intimal thickening, and the intima/media area ratio was 0.209 ± 0.058 (p = 0.094). This ratio was 0.287 ± 0.048 (p = 0.902) when pravastatin was administered alone, indicating that it had no significant effect on intimal thickening. The ratio was 0.175 ± 0.041 (p = 0.042) when both EPA-E and pravastatin were administered, indicating that this combination had a significant inhibitory effect on intimai thickening in the cuffsheathed region. These findings suggest that combined treatment with EPA-E and pravastatin is more effective than respective monotherapies in lowering serum lipids and/or preventing an intimal thickening as events of atherogenesis.