Study on the Mechanism of Allopurinol Inhibiting the Lipid Accumulation of Macrophages
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Affiliation:

1.Department of Integrated Medicine, the Affiliated Dongfeng Hospital, ;2.College of Basic Medicine, Hubei University of Medicine, Shiyan, Hubei 442000, China)

Clc Number:

R363

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    Abstract:

    Aim To construct the mouse macrophage foam model by using oxidized low density lipoprotein(ox-LDL); To investigate the effect of allopurinol on lipid accumulation in macrophage foam process and its mechanism. Methods Mouse macrophage cell line RAW264.7 was cultured in vitro, and foam model was constructed by using ox-LDL or Dil-ox-LDL incubating macrophage cells. Macrophage cells were treated with different concentrations of allopurinol, and MTT method was used to screen the suitable experimental concentration. Macrophage cells were treated with suitable concentration of allopurinol. After Dil-ox-LDL incubation, the lipid accumulation in RAW264.7 cells was observed under confocal fluorescence microscopy. The change of total cholesterol in the cells was detected by enzymatic end point method.Semi-quantitative, fluorescence quantitative RT-PCR and Western blot were used to detect the expressions of liver X receptor α(LXRα), ATP-binding cassette transporter A1(ABCA1) mRNA and protein in cells. Results Compared with the ox-LDL induced foam model group, the lipid accumulation and total cholesterol content were significantly decreased in RAW264.7 cells of the allopurinol group. Allopurinol could cause the high expressions of LXRα, ABCA1 mRNA and protein. Conclusion Allopurinol can restrain mouse macrophage foam process induced by ox-LDL, and regulate intracellular cholesterol content through the up-regulation of LXRα-ABCA1 pathway.

    Reference
    [1] Thorp E, Tabas I.Mechanisms and consequences of efferocytosis in advanced atherosclerosis.J Leukoc Biol, 2009, 86(5): 1 089-095.
    [2] Andrés V, Pello OM, Silvestre-Roig C.Macrophage proliferation and apoptosis in atherosclerosis.Curr Opin Lipidol, 2012, 23(5): 429-438.
    [3] Betowski J.Liver X receptors(LXR) as therapeutic targets in dyslipidemia.Cardiovasc Ther, 2008, 26(4): 297-316.
    [4] Voloshyna I, Reiss AB.The ABC transporters in lipid flux and atherosclerosis.Prog Lipid Res, 2011, 50(3): 213-224.
    [5] Kushiyama A, Okubo H, Sakoda H, et al.Xanthine oxidoreductase is involved in macrophage foam cell formation and atherosclerosis development.Arterioscler Thromb Vasc Biol, 2012, 32(2): 291-298.
    [6] Tiwari RL, Singh V, Barthwal MK.Macrophages: an elusive yet emerging therapeutic target of atherosclerosis.Med Res Rev, 2008, 28(4): 483-544.
    [7] Noman A, Ang DS, Ogston S, et al.Effect of high-dose allopurinol on exercise in patients with chronic stable angina: a randomised, placebo controlled crossover trial.Lancet, 2010, 375(9732): 2 161-167.
    [8] Grimaldi-Bensouda L, Alpérovitch A, Aubrun E, et al.Impact of allopurinol on risk of myocardial infarction.Ann Rheum Dis, 2015, 74(5): 836-842.
    [9] Francisco J, Miguel J, Antonio R, et al.Allopurinol use and risk of non-fatal acute myocardial infarction.Heart, 2015, 101(9): 679-685.
    [10] Hopkins P.Molecular biology of atherosclerosis.Physiol Rev, 2013, 93(3): 1 317-342.
    [11] Zhang Y, Beyer TP, Bramlett KS, et al.Liver X receptor and retinoic X receptor mediated ABCA1 regulation and cholesterol efflux in macrophage cells-messenger RNA measured by branched DNA technology.Mol Genet Metab, 2002, 77(1-2): 150-158.
    [12] Zhao C, Dahlman-Wright K.Liver X receptor in cholesterol metabolism.J Endocrinol, 2010, 204(3): 233-240.
    [13] Zhou X, Yin Z, Guo X, et al.Inhibition of ERK1/2 and activation of liver X receptor synergistically induce macrophage ABCA1 expression and cholesterol efflux.J Biol Chem, 2010, 285(9): 6 316-326.
    [14] Mallat Z.Macrophages.Arterioscler Thromb Vasc Biol, 2014, 34(12): 2 509-519.
    [15] Zimmer S, Grebe A, Latz E.Danger signaling in atherosclerosis.Circ Res, 2015, 116(2): 323-340.
    [16] Tall AR, Yvan-Charvet L, Terasaka N, et al.HDL, ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis.Cell Metab, 2008, 7(5): 365-375.
    [17] Reddy ST, Hama S, Ng C, et al.ATP-binding cassette transporter 1 participates in LDL oxidation by artery wall cells.Arterioscler Thromb Vasc Bio, 2002, 22(11): 1 877-883.
    [18] Tang CK, Yi GH, Yang JH, et al.Oxidized LDL upregulated ATP binding cassette transporter-1 in THP-1 macrophages.Acta Pharmacol Sin, 2004, 25(5): 581-586.
    [19] 薛偕华, 魏伟, 陈彤, 等.泽泻汤对巨噬细胞泡沫化脂质沉积及其LXRα和ABCA1表达的影响.中国动脉硬化杂志, 2013, 21(11): 971-976.
    [20] 吕运成, 王佐, 姚峰, 等.薯蓣皂苷元对THP-1巨噬细胞ABCA1表达及胆固醇流出的影响.中国动脉硬化杂志, 2014, 22(7): 680-684.
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ZHENG Wei, CHEN Xin, LI Ya-Xin, LI Shan. Study on the Mechanism of Allopurinol Inhibiting the Lipid Accumulation of Macrophages[J]. Editorial Office of Chinese Journal of Arteriosclerosis,2016,24(4):355-360.

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History
  • Received:February 05,2015
  • Revised:December 23,2015
  • Online: June 30,2016
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