5-(4-Hydroxy-2,3,5-trimethylbenzylidene) thiazolidine-2,4-dione attenuates atherosclerosis possibly by reducing monocyte recruitment to the lesion

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

Research output: Contribution to journalArticle

11 Citations (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.

Original languageEnglish
Pages (from-to)471-478
Number of pages8
JournalExperimental and Molecular Medicine
Volume43
Issue number8
DOIs
Publication statusPublished - 2011 Aug 31

Keywords

  • Antioxidants
  • Arachidonate 5-lipoxygenase
  • Atherosclerosis
  • Endothelial cells
  • Macrophages

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Clinical Biochemistry

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    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. (2011). 5-(4-Hydroxy-2,3,5-trimethylbenzylidene) thiazolidine-2,4-dione attenuates atherosclerosis possibly by reducing monocyte recruitment to the lesion. Experimental and Molecular Medicine, 43(8), 471-478. https://doi.org/10.3858/emm.2011.43.8.053