Acipimox attenuates atherosclerosis and enhances plaque stability in ApoE-deficient mice fed a palmitate-rich diet

Saturated fatty acids (FA) have been linked to an increased risk of cardiovascular disease. The effects of acipimox, a FA-lowering agent, on palmitate- (an important saturated fatty acid) stimulated atherosclerosis remains to be elucidated. We investigated the effects of acipimox on atherosclerosis in ApoE−/− mice fed a palmitate-rich diet. Male ApoE−/− mice, 6–8 weeks of age, were randomized into three groups. The animals were fed a normal chow diet in the control group, a diet containing 5% palmitic acid in the palmitate group, and a diet containing 5% palmitic acid and 0.02% acipimox in the acipimox group. The plasma lipid profiles, aortic lesions, plaque collagen content and the expression of matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, and MMP-14 and the tissue inhibitor of MMP (TIMP)-1, and TIMP-2 were determined after a 12-week treatment. The palmitate-rich diet significantly increased plasma FA concentrations (P < 0.01), enhanced atherosclerotic lesions (P < 0.01), decreased plaque collagen content (P < 0.01) and upregulated MMP-2 (P < 0.05) in the aorta. Additionally, all of these harmful effects were significantly attenuated by co-treatment with acipimox (P < 0.05 or P < 0.01). The present study suggests that acipimox attenuates atherosclerosis and enhances plaque stability in ApoE−/− mice fed a palmitate-rich diet.

► A palmitate-rich diet enhances atherosclerosis and promotes plaque instability.
► A palmitate-rich diet upregulates MMP-2 in aorta.
► Acipimox attenuates atherosclerosis in ApoE−/− mice fed a palmitate-rich diet.
► Acipimox enhances plaque stability in ApoE−/− mice fed a palmitate-rich diet.
► Acipimox attenuates palmitate-induced upregulation of MMP-2.