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Anti-atherogenic effect of BHB-TZD having inhibitory activities on cyclooxygenase and 5-lipoxygenase in hyperlipidemic mice

Title
Anti-atherogenic effect of BHB-TZD having inhibitory activities on cyclooxygenase and 5-lipoxygenase in hyperlipidemic mice
Authors
Choi J.-H.Jeon H.J.Park J.-G.Sonn S.K.Lee M.-R.Lee M.-N.You H.J.Kim G.-Y.Kim J.-H.Lee M.H.Kwon O.-S.Nam K.-H.Kim H.-C.Jeong T.-S.Lee W.S.Oh G.T.
Ewha Authors
오구택손성근이미니
SCOPUS Author ID
오구택scopus; 손성근scopus; 이미니scopusscopus
Issue Date
2010
Journal Title
Atherosclerosis
ISSN
0021-9150JCR Link
Citation
vol. 212, no. 1, pp. 146 - 152
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Cyclooxygenase (COX) and 5-lipoxygenase (5-LOX), which play pivotal roles in atherogenesis, have been reported to be involved in plaque stability. Licofelone, a dual COX and 5-LOX inhibitor, has been reported to possess anti-atherogenic effect in rabbit atherosclerosis model. We therefore investigated the anti-atherogenic effect of BHB-TZD [5-(3,5-di-tert-butyl-4-hydroxybenzylidene)thiazolidin-2,4-dione], a dual COX and 5-LOX inhibitor, in low density lipoprotein receptor null (LDLR-/-) mice. Fifteen LDLR-/- mice were fed a western diet (control group), whereas 15 were fed a western diet plus 0.1% (w/w) BHB-TZD (BHB-TZD group). After 8 weeks, the BHB-TZD group had markedly lower serum levels of leukotriene B4 and prostaglandin E2 than the control group. Interestingly, BHB-TZD treatment also reduced plasma triglyceride level without significant changes in total cholesterol and HDL levels. Compared with control mice, BHB-TZD fed mice had 52% fewer fatty streak lesions in the aortic sinus, as well as fewer initial lesions in the aortic arch. Macrophage infiltration into the lesions was 40% lower, and collagen and smooth muscle cells were increased by 102% and 96%, respectively, in the BHB-TZD group compared with the control group. In addition, aortic expression of proatherogenic molecules including TNF-α, IL-1β, IL-6, MCP-1 and VCAM-1, was lower in the BHB-TZD group than the control group. BHB-TZD treatment also reduced MMP-2 and MMP-9 expressions in aorta. In conclusion, BHB-TZD effectively attenuated atherosclerosis in mouse model, suggesting its therapeutic potential for atherosclerosis. © 2010 Elsevier Ireland Ltd.
DOI
10.1016/j.atherosclerosis.2010.05.003
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자연과학대학 > 생명과학전공 > Journal papers
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