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

Jae Hoon Choi, Hyung Jun Jeon, Jong Gil Park, Seong Keun Sonn, Mi Ran Lee, Mi Ni Lee, Hye Jin You, Geun Young Kim, Jae Hong Kim, Mun Han Lee, Oh Seung Kwon, Ki Hoan Nam, Hyoung Chin Kim, Tae Sook Jeong, Woo Song Lee, Goo Taeg Oh

Research output: Contribution to journalArticle

15 Citations (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.

Original languageEnglish
Pages (from-to)146-152
Number of pages7
JournalAtherosclerosis
Volume212
Issue number1
DOIs
Publication statusPublished - 2010 Sep

Keywords

  • 5-Lipoxygenase
  • Atherosclerosis
  • BHB-TZD
  • Cyclooxygenase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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  • Cite this

    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. (2010). Anti-atherogenic effect of BHB-TZD having inhibitory activities on cyclooxygenase and 5-lipoxygenase in hyperlipidemic mice. Atherosclerosis, 212(1), 146-152. https://doi.org/10.1016/j.atherosclerosis.2010.05.003