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Cilostazol reduces atherosclerosis by inhibition of superoxide and tumor necrosis factor-α formation in low-density lipoprotein receptor-null mice fed high cholesterol
- Title
- Cilostazol reduces atherosclerosis by inhibition of superoxide and tumor necrosis factor-α formation in low-density lipoprotein receptor-null mice fed high cholesterol
- Authors
- Lee J.H.; Oh G.T.; Park S.Y.; Choi J.-H.; Park J.-G.; Kim C.D.; Lee W.S.; Rhim B.Y.; Shin Y.W.; Hong K.W.
- Ewha Authors
- 오구택
- SCOPUS Author ID
- 오구택
- Issue Date
- 2005
- Journal Title
- Journal of Pharmacology and Experimental Therapeutics
- ISSN
- 0022-3565
- Citation
- Journal of Pharmacology and Experimental Therapeutics vol. 313, no. 2, pp. 502 - 509
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- Abstract
- This study shows that 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxy]-3,4-dihydro-2(1H)-quinolinone (cilostazol) suppresses the atherosclerotic lesion formation in the low-density lipoprotein receptor (Ldlr)-null mice. Ldlr-null mice fed a high cholesterol diet showed multiple plaque lesions in the proximal ascending aorta including aortic sinus, accompanied by increased macrophage accumulation with increased expression of vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1). Supplementation of cilostazol (0.2% w/w) in diet significantly decreased the plaque lesions with reduced macrophage accumulation and suppression of VCAM-1 and MCP-1 in situ. Increased superoxide and tumor necrosis factor-α (TNF-α) production were significantly lowered by cilostazol in situ as well as in cultured human umbilical vein endothelial cells (HUVECs). TNF-α-induced increased inhibitory κBα degradation in the cytoplasm and nuclear factor-κB (NF-κB) p65 activation in the nuclei of HUVECs were reversed by cilostazol (1 ∼ 100 μM) as well as by (E)-3[(4-t-butylphenyl)sulfonyl]-2-propenenitrile (BAY 11-7085) (10 μM), suggesting that cilostazol strongly inhibits NF-κB activation and p65 translocation into the nuclei. Furthermore, in gel shift and DNA-binding assay, cilostazol inhibited NF-κB/DNA complex and nuclear DNA-binding activity of the NF-κB in the nuclear extracts of the RAW 264.7 cells. Taken together, it is suggested that the antiatherogenic effect of cilostazol in cholesterol-fed Ldlr-null mice is ascribed to its property to suppress superoxide and TNF-α formation, and thereby reducing NF-κB activation/transcription, VCAM-1/MCP-1 expressions, and monocyte recruitments. Copyright © 2005 by The American Society for Pharmacology and Experimental Therapeutics.
- DOI
- 10.1124/jpet.104.079780
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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