A selective NFkB inhibitor, DHMEQ, reduced atherosclerosis in ApoE-deficient mice

被引:38
作者
Chiba, Tsuyoshi
Kondo, Yoshitaka
Shinozaki, Shohei
Kaneko, Eiji
Ishigami, Akihito
Maruyama, Naoki
Umezawa, Kazuo
Shimokado, Kentaro
机构
[1] Tokyo Med & Dent Univ, Grad Sch, Bunkyo Ku, Tokyo 1138619, Japan
[2] Tokyo Metropolitan Inst Gerontol, Tokyo, Japan
[3] Keio Univ, Fac Sci & Technol, Dept Appl Chem, Tokyo 108, Japan
关键词
inflammation; hyperlipidemia; TNF-alpha;
D O I
10.5551/jat.13.308
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Background and Purpose: Atherosclerosis is a chronic inflammatory process, and anti-inflammatory agents potentially inhibit the development of atherosclerosis. We tested whether a novel NFkB inhibitor reduces atherosclerosis. Methods: Dehydroxymethylepoxyquinomicin (10 mg/kg) or vehicle (chloromethyl cellulose) was injected intraperitoneally into apoE-deficient mice three times a week for 16 weeks. The entire aorta was excised and atherosclerotic area was determined at 4 and 16 weeks. Serum levels of cholesterol, triglyceride, TNF-alpha and adiponectin were also measured. Results: The atherosclerotic area was significantly smaller in mice treated with dehydroxymethyl-epoxyquinomicin both at 4 and 16 weeks. There was no significant difference in body weight or serum levels of cholesterol, triglyceride, and adiponectin. Conclusions: A new NFkB inhibitor, dehydroxymethylepoxyquinomicin, reduced atherosclerosis without affecting plasma lipid levels in apoE-deficient mice.
引用
收藏
页码:308 / 313
页数:6
相关论文
共 29 条
  • [1] Tumor necrosis factor-α induces fractalkine expression preferentially in arterial endothelial cells and mithramycin A suppresses TNF-α-induced fractalkine expression
    Ahn, SY
    Cho, CH
    Park, KY
    Lee, HJ
    Lee, S
    Park, SK
    Lee, IK
    Koh, GY
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2004, 164 (05) : 1663 - 1672
  • [2] Inhibition of tumor necrosis factor-α-induced nuclear translocation and activation of NF-κB by dehydroxymethylepoxyquinomicin
    Ariga, A
    Namekawa, J
    Matsumoto, N
    Inoue, J
    Umezawa, K
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (27) : 24625 - 24630
  • [3] Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion
    Brand, K
    Page, S
    Rogler, G
    Bartsch, A
    Brandl, R
    Knuechel, R
    Page, M
    Kaltschmidt, C
    Baeuerle, PA
    Neumeier, D
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1996, 97 (07) : 1715 - 1722
  • [4] Activation of nuclear factor-κB significantly contributes to lumen loss in a rabbit iliac artery balloon angioplasty model
    Breuss, JM
    Cejna, M
    Bergmeister, H
    Kadl, A
    Baumgartl, G
    Steurer, S
    Xu, Z
    Koshelnick, Y
    Lipp, J
    De Martin, R
    Losert, U
    Lammer, J
    Binder, BR
    [J]. CIRCULATION, 2002, 105 (05) : 633 - 638
  • [5] Nuclear factor-kappa B activity and arterial response to balloon injury
    Cercek, B
    Yamashita, M
    Dimayuga, P
    Zhu, J
    Fishbein, MC
    Kaul, S
    Shah, PK
    Nilsson, J
    Regnstrom, J
    [J]. ATHEROSCLEROSIS, 1997, 131 (01) : 59 - 66
  • [6] Novel Antiinflammatory vascular benefits of systemic and stent-based delivery of ethylisopropylamiloride
    Chen, YX
    Ma, XL
    Whitman, S
    O'Brien, ER
    [J]. CIRCULATION, 2004, 110 (24) : 3721 - 3726
  • [7] Current and future treatment of hyperlipidemia: The role of statins
    Farnier, M
    Davignon, J
    [J]. AMERICAN JOURNAL OF CARDIOLOGY, 1998, 82 (4B) : 3J - 10J
  • [8] Rosuvastatin reduces MMP-7 secretion by human monocyte-derived macrophages: potential relevance to atherosclerotic plaque stability
    Furman, C
    Copin, C
    Kandoussi, M
    Davidson, R
    Moreau, M
    McTaggart, B
    Chapman, MJ
    Fruchart, JC
    Rouis, M
    [J]. ATHEROSCLEROSIS, 2004, 174 (01) : 93 - 98
  • [9] Tumor necrosis factor-α and troglitazone regulate plasminogen activator inhibitor type 1 production through extracellular signal-regulated kinase- and nuclear factor-κB-dependent pathways in cultured human umbilical vein endothelial cells
    Hamaguchi, E
    Takamura, T
    Shimizu, A
    Nagai, Y
    [J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2003, 307 (03) : 987 - 994
  • [10] Simvastatin reduces NF-κB activity in peripheral mononuclear and in plaque cells of rabbit atheroma more markedly than lipid lowering diet
    Hernández-Presa, MA
    Ortego, M
    Tuñón, J
    Martín-Ventura, JL
    Mas, S
    Blanco-Colio, LM
    Aparicio, C
    Ortega, L
    Gómez-Gerique, J
    Vivanco, F
    Egido, J
    [J]. CARDIOVASCULAR RESEARCH, 2003, 57 (01) : 168 - 177