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 2024-01-20T18:34:04Z 2024-01-20T18:34:04Z 2021-09-05 2010-09 0021-9150 https://pubs.kist.re.kr/handle/201004/131138 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-alpha, IL-1 beta, 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. (C) 2010 Elsevier Ireland Ltd. All rights reserved. English ELSEVIER IRELAND LTD Anti-atherogenic effect of BHB-TZD having inhibitory activities on cyclooxygenase and 5-lipoxygenase in hyperlipidemic mice Article 10.1016/j.atherosclerosis.2010.05.003 1 ATHEROSCLEROSIS, v.212, no.1, pp.146 - 152 ATHEROSCLEROSIS 212 1 146 152 N scie scopus 000281459900023 2-s2.0-77956232311 Cardiac & Cardiovascular Systems Peripheral Vascular Disease Cardiovascular System & Cardiology Article DEFICIENT MICE ATHEROSCLEROSIS PLAQUE PROSTACYCLIN INFLAMMATION MECHANISMS EXPRESSION PATHWAY DISEASE WALL BHB-TZD Atherosclerosis Cyclooxygenase 5-Lipoxygenase