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KMID : 0620920110430080471
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Experimental & Molecular Medicine
2011 Volume.43 No. 8 p.471 ~ p.478
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5-(4-Hydroxy-2,3,5-trimethylbenzylidene) thiazolidine-2,4-dione attenuates atherosclerosis possibly by reducing monocyte recruitment to the lesion
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Choi Jae-Hoon
Park Jong-Gil
Jeon Hyung-Jun
Kim Mi-Sun
Lee Mi-Ran
Lee Mi-Ni
Sonn Seong-Keun
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
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Abstract
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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.
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KEYWORD
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antioxidants, arachidonate 5-lipoxygenase, atherosclerosis, endothelial cells, macrophages
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