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.
Department of Cardiology, General Hospital of PLA Chengdu Military Area Command, Chengdu, Sichuan 610083, PR China.
Feipeng
F
Jin
Sihua
S
Jiang
Dachun
D
Yang
Xingmei
X
Zhang
Yun
Y
Yang
Yan
Y
Zhang
Kun
K
Li
Yongjian
Y
Yang
Shuangtao
S
Ma
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology* / Q000517:prevention & control*; D004036:Diet, Atherogenic / Q000009:adverse effects*; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D010168:Palmitates / Q000008:administration & dosage / Q000009:adverse effects*; D058226:Plaque, Atherosclerotic / Q000473:pathology*; D011719:Pyrazines / Q000008:administration & dosage*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D001057:Apolipoproteins E; D000960:Hypolipidemic Agents; D010168:Palmitates; D011719:Pyrazines; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D053511:Matrix Metalloproteinase 14; C027696:acipimox