title: 5-(4-Hydroxy-2,3,5-trimethylbenzylidene) thiazolidine-2,4-dione attenuates atherosclerosis possibly by reducing monocyte recruitment to the lesion.
abstract: 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 B4 (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-α) 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-α , 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.
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Choi
authors.forename: Jong-Gil
authors.initials: JG
authors.lastname: Park
authors.forename: Hyung Jun
authors.initials: HJ
authors.lastname: Jeon
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Mi-Ran
authors.initials: MR
authors.lastname: Lee
authors.forename: Mi-Ni
authors.initials: MN
authors.lastname: Lee
authors.forename: SeongKeun
authors.initials: S
authors.lastname: Sonn
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Kim
authors.forename: Mun Han
authors.initials: MH
authors.lastname: Lee
authors.forename: Myung-Sook
authors.initials: MS
authors.lastname: Choi
authors.forename: Yong Bok
authors.initials: YB
authors.lastname: Park
authors.forename: Oh-Seung
authors.initials: OS
authors.lastname: Kwon
authors.forename: Tae-Sook
authors.initials: TS
authors.lastname: Jeong
authors.forename: Woo Song
authors.initials: WS
authors.lastname: Lee
authors.forename: Hyun Bo
authors.initials: HB
authors.lastname: Shim
authors.forename: Dong Hae
authors.initials: DH
authors.lastname: Shin
authors.forename: Goo Taeg
authors.initials: GT
authors.lastname: Oh
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D011897:Random Allocation; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D018932:Chemokine CCL2; D011973:Receptors, LDL; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; C500090:thiazolidine-2,4-dione; D007975:Leukotriene B4; D015232:Dinoprostone