Choi, Jae-Hoon Park, Jong-Gil Jeon, Hyung Jun Kim, Mi-Sun Lee, Mi-Ran Lee, Mi-Ni Sonn, SeongKeun Kim, Jae-Hong Lee, Mun Han Choi, Myung-Sook Park, Yong Bok Kwon, Oh-Seung Jeong, Tae-Sook Lee, Woo Song Shim, Hyun Bo Shin, Dong Hae Oh, Goo Taeg 2024-01-20T16:33:06Z 2024-01-20T16:33:06Z 2021-09-05 2011-08 1226-3613 https://pubs.kist.re.kr/handle/201004/130122 A variety of benzylidenethiazole analogs have been demonstrated to inhibit 5-lipoxygenase (5-LOX). Here we report the anti-atherogenic potential of 5-(4-hydroxy-2,3,5-trimethylbenzylidene) thiazolidin-2,4-dione (HMB-TZD), a benzylidenethiazole analog, and its potential mechanism of action in LDL receptor-deficient (Ldlr(-/-)) mice. HMB-TZD Treatment reduced leukotriene B-4 (LTB4) production significantly in RAW264.7 macrophages and SVEC4-10 endothelial cells. Macrophages or endothelial cells pre-incubated with HMB-TZD for 2 h and then stimulated with lipopolysaccharide or tumor necrosis factor-alpha (TNF-alpha) displayed reduced cytokine production. Also, HMB-TZD reduced cell migration and adhesion in accordance with decreased proinflammatory molecule production in vitro and ex vivo. HMB-TZD treatment of 8-week-old male Ldlr(-/-) mice resulted in significantly reduced atherosclerotic lesions without a change to plasma lipid profiles. Moreover, aortic expression of pro-atherogenic molecules involved in the recruitment of monocytes to the aortic wall, including TNF-alpha, MCP-1, and VCAM-1, was downregulated. HMB-TZD also reduced macrophage infiltration into atherosclerotic lesions. In conclusion, HMB-TZD ameliorates atherosclerotic lesion formation possibly by reducing the expression of proinflammatory molecules and monocyte/macrophage recruitment to the lesion. These results suggest that HMB-TZD, and benzylidenethiazole analogs in general, may have therapeutic potential as treatments for atherosclerosis. English 생화학분자생물학회 5-(4-Hyd roxy-2,3,5-tri methylbenzylidene) thiazolidine-2,4-dione attenuates atherosclerosis possibly by reducing monocyte recruitment to the lesion Article 10.3858/emm.2011.43.8.053 1 Experimental & Molecular Medicine, v.43, no.8, pp.471 - 478 Experimental & Molecular Medicine 43 8 471 478 N scie scopus kci ART001577603 000294400000005 2-s2.0-80052164898 Biochemistry & Molecular Biology Medicine, Research & Experimental Biochemistry & Molecular Biology Research & Experimental Medicine Article KAPPA-B PATHWAY 5-LIPOXYGENASE PATHWAY OXIDATIVE STRESS LEUKOTRIENE B-4 CYCLOOXYGENASE INHIBITION RECEPTOR MECHANISMS BLT1 WALL antioxidants arachidonate 5-lipoxygenase atherosclerosis endothelial cells macrophages