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

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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 1

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Arachidonate 5-Lipoxygenase
Prostaglandin-Endoperoxide Synthases
Atherosclerosis
Lipoxygenase Inhibitors
Control Groups
licofelone
LDL Receptors
Matrix Metalloproteinases
Sinus of Valsalva
Leukotriene B4
Vascular Cell Adhesion Molecule-1
Thoracic Aorta
Interleukin-1
Dinoprostone
HDL Cholesterol
Smooth Muscle Myocytes
Aorta
Interleukin-6
Triglycerides
Collagen

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Anti-atherogenic effect of BHB-TZD having inhibitory activities on cyclooxygenase and 5-lipoxygenase in hyperlipidemic mice. / Choi, Jae Hoon; Jeon, Hyung Jun; Park, Jong Gil; Sonn, Seong Keun; Lee, Mi Ran; Lee, Mi Ni; You, Hye Jin; Kim, Geun Young; Kim, Jae-Hong; Lee, Mun Han; Kwon, Oh Seung; Nam, Ki Hoan; Kim, Hyoung Chin; Jeong, Tae Sook; Lee, Woo Song; Oh, Goo Taeg.

In: Atherosclerosis, Vol. 212, No. 1, 01.09.2010, p. 146-152.

Research output: Contribution to journalArticle

Choi, JH, Jeon, HJ, Park, JG, Sonn, SK, Lee, MR, Lee, MN, You, HJ, Kim, GY, Kim, J-H, Lee, MH, Kwon, OS, Nam, KH, Kim, HC, Jeong, TS, Lee, WS & Oh, GT 2010, 'Anti-atherogenic effect of BHB-TZD having inhibitory activities on cyclooxygenase and 5-lipoxygenase in hyperlipidemic mice', Atherosclerosis, vol. 212, no. 1, pp. 146-152. https://doi.org/10.1016/j.atherosclerosis.2010.05.003
Choi, Jae Hoon ; Jeon, Hyung Jun ; Park, Jong Gil ; Sonn, Seong Keun ; Lee, Mi Ran ; Lee, Mi Ni ; You, Hye Jin ; Kim, Geun Young ; Kim, Jae-Hong ; Lee, Mun Han ; Kwon, Oh Seung ; Nam, Ki Hoan ; Kim, Hyoung Chin ; Jeong, Tae Sook ; Lee, Woo Song ; Oh, Goo Taeg. / Anti-atherogenic effect of BHB-TZD having inhibitory activities on cyclooxygenase and 5-lipoxygenase in hyperlipidemic mice. In: Atherosclerosis. 2010 ; Vol. 212, No. 1. pp. 146-152.
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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.",
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AU - Sonn, Seong Keun

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AU - You, Hye Jin

AU - Kim, Geun Young

AU - Kim, Jae-Hong

AU - Lee, Mun Han

AU - Kwon, Oh Seung

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