5-(4-Hydroxy-2,3,5-trimethylbenzylidene) thiazolidine-2,4-dione attenuates atherosclerosis possibly by reducing monocyte recruitment to the lesion.
10.3858/emm.2011.43.8.053
- Author:
Jae Hoon CHOI
1
;
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
Author Information
1. Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
antioxidants;
arachidonate 5-lipoxygenase;
atherosclerosis;
endothelial cells;
macrophages
- MeSH:
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
- From:Experimental & Molecular Medicine
2011;43(8):471-478
- CountryRepublic of Korea
- Language:English
-
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.
