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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

Title
5-(4-Hydroxy-2,3,5-trimethylbenzylidene) thiazolidine-2,4-dione attenuates atherosclerosis possibly by reducing monocyte recruitment to the lesion
Authors
Choi J.-H.Park J.-G.Jeon H.J.Kim M.-S.Lee M.-R.Lee M.-N.Sonn S.Kim J.-H.Lee M.H.Choi M.-S.Park Y.B.Kwon O.-S.Jeong T.-S.Lee W.S.Shim H.B.Shin D.H.Oh G.T.
Ewha Authors
오구택신동해심현보손성근이미니
SCOPUS Author ID
오구택scopus; 신동해scopus; 심현보scopus; 손성근scopus; 이미니scopusscopus
Issue Date
2011
Journal Title
Experimental and Molecular Medicine
ISSN
1226-3613JCR Link
Citation
vol. 43, no. 8, pp. 471 - 478
Indexed
SCI; SCIE; SCOPUS; KCI WOS scopus
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 B 4 (LTB 4) 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.
DOI
10.3858/emm.2011.43.8.053
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자연과학대학 > 생명과학전공 > Journal papers
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