Exp Mol Med.
2011 Aug;43(8):471-478. 10.3858/emm.2011.43.8.053.
5-(4-Hydroxy-2,3,5-trimethylbenzylidene) thiazolidine-2,4-dione attenuates atherosclerosis possibly by reducing monocyte recruitment to the lesion
- Affiliations
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- 1Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Korea.
- 2Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea. gootaeg@ewha.ac.kr
- 3Department of Veterinary Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.
- 4Division of Life and Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea.
- 5School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
- 6Department of Food Science and Nutrition, Kyungbook National University, Daegu 702-701, Korea.
- 7Department of Genetic Engineering, Kyungbook National University, Daegu 702-701, Korea.
- 8Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, Seoul 136-791, Korea.
- 9National Research Laboratory of Lipid Metabolism & Atherosclerosis, KRIBB, Daejeon 305-806, Korea.
- 10Bioindustry Technology Research Center, KRIBB, Jeongeup 580-185, Korea.
- KMID: 1022122
- DOI: http://doi.org/10.3858/emm.2011.43.8.053
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-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.
MeSH Terms
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Animals
Atherosclerosis/*drug therapy
Cell Adhesion/drug effects
Cell Line
Cell Movement/drug effects
Chemokine CCL2/metabolism
Dinoprostone/metabolism
Enzyme-Linked Immunosorbent Assay
Humans
Leukotriene B4/metabolism
Macrophages/cytology/drug effects
Male
Mice
Monocytes/cytology/*drug effects
Random Allocation
Receptors, LDL/deficiency/genetics
Thiazolidinediones/*therapeutic use
Tumor Necrosis Factor-alpha/pharmacology
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