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

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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

Fingerprint

Macrophages
Monocytes
Atherosclerosis
LDL Receptors
Endothelial cells
Molecules
Endothelial Cells
Tumor Necrosis Factor-alpha
Arachidonate 5-Lipoxygenase
Leukotriene B4
Vascular Cell Adhesion Molecule-1
Infiltration
Cell Adhesion
Action Potentials
Cell Movement
Lipopolysaccharides
Down-Regulation
Adhesion
Cytokines
Lipids

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Clinical Biochemistry

Cite this

5-(4-Hydroxy-2,3,5-trimethylbenzylidene) thiazolidine-2,4-dione attenuates atherosclerosis possibly by reducing monocyte recruitment to the lesion. / Choi, Jae Hoon; Park, Jong Gil; Jeon, Hyung Jun; Kim, Mi Sun; Lee, Mi Ran; Lee, Mi Ni; Sonn, Seongkeun; Kim, Jae-Hong; Lee, Mun Han; Choi, Myung Sook; Park, Yong Bok; Kwon, Oh Seung; Jeong, Tae Sook; Lee, Woo Song; Shim, Hyun Bo; Shin, Dong Hae; Oh, Goo Taeg.

In: Experimental and Molecular Medicine, Vol. 43, No. 8, 31.08.2011, p. 471-478.

Research output: Contribution to journalArticle

Choi, JH, Park, JG, Jeon, HJ, Kim, MS, Lee, MR, Lee, MN, Sonn, S, Kim, J-H, Lee, MH, Choi, MS, Park, YB, Kwon, OS, Jeong, TS, Lee, WS, Shim, HB, Shin, DH & Oh, GT 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, vol. 43, no. 8, pp. 471-478. https://doi.org/10.3858/emm.2011.43.8.053
Choi, Jae Hoon ; Park, Jong Gil ; Jeon, Hyung Jun ; Kim, Mi Sun ; Lee, Mi Ran ; Lee, Mi Ni ; Sonn, Seongkeun ; Kim, Jae-Hong ; Lee, Mun Han ; Choi, Myung Sook ; Park, Yong Bok ; Kwon, Oh Seung ; Jeong, Tae Sook ; Lee, Woo Song ; Shim, Hyun Bo ; Shin, Dong Hae ; Oh, Goo Taeg. / 5-(4-Hydroxy-2,3,5-trimethylbenzylidene) thiazolidine-2,4-dione attenuates atherosclerosis possibly by reducing monocyte recruitment to the lesion. In: Experimental and Molecular Medicine. 2011 ; Vol. 43, No. 8. pp. 471-478.
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AU - Park, Jong Gil

AU - Jeon, Hyung Jun

AU - Kim, Mi Sun

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