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: Jae-Hoon Choi, Jong-Gil Park, Hyung Jun Jeon, Mi-Sun Kim, Mi-Ran Lee, Mi-Ni Lee, SeongKeun Sonn, Jae-Hong Kim, Mun Han Lee, Myung-Sook Choi, Yong Bok Park, Oh-Seung Kwon, Tae-Sook Jeong, Woo Song Lee, Hyun Bo Shim, Dong Hae Shin, Goo Taeg Oh
• Journal: Experimental & molecular medicine (Exp Mol Med) Vol. 43 Issue 8 Pg. 471-8 (Aug 31 2011) ISSN: 2092-6413 [Electronic] United States
• PMID: 21691142 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CCL2
• Receptors, LDL
• Thiazolidinediones
• Tumor Necrosis Factor-alpha
• thiazolidine-2,4-dione
• Leukotriene B4
• Dinoprostone

Topics

• 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)