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The expression of ABCG1 transporter gene in peripheral blood mononuclear cells of patients with atherosclerosis

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Abstract

The antiatherogenic role of high-density lipoproteins (HDL) was demonstrated by numerous experimental, clinical and epidemiological studies. The mechanism underlying the antiatherogenic potential of HDL is based on their involvement in reverse cholesterol transport (RCT) from peripheral tissues into the liver. Transmembrane transporter ABCG1 is a key RCT protein. Its function is to remove cholesterol from cells and transfer it to HDL. The role of ABCG1 transporter in the development of atherosclerosis in humans remains unexplored. The goal of our study was to investigate the expression of ABCG1 gene in patients with atherosclerosis. Real-time PCR was applied to study ABCG1 mRNA content in leukocytes, monocytes, and macrophages activated with macrophage colony-stimulating factor (M-CSF) from patients with atherosclerosis and healthy people. The amount of ABCG1 protein in monocytes and macrophages of patients and healthy donors was assayed by immunoblotting. It was found that the level of ABCG1 mRNA (p < 0.001) and ABCG1 protein (p < 0.05) was lower in macrophages of patients with atherosclerosis. The level of ABCG1 mRNA in monocytes of patients with artery occlusion was lower than in patients with features of lesser stenosis and the control group (p < 0.05). No correlation was found between ABCG1 gene expression and total and HDL cholesterol levels in the blood plasma. It can be concluded that reduced ABCG1 gene expression in monocytes and macrophages may be critical for the atherosclerosis progression.

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Abbreviations

ABCG1:

ATP-binding cassette transporter G1

HDL:

high-density lipoproteins

RCT:

reverse cholesterol transport

TC:

total cholesterol

C HDL :

HDL cholesterol

CLDL :

LDL cholesterol

TG:

triglycerides

M-CSF:

macrophage colony-stimulating factor

References

  • Barter, P., Gotto, A.M., La, Rosa, J.C., Maroni, J., Szarek, M., Grundy, S.M., Kastelein, J.J., Bittner, V., and Fruchart, J.C., HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events, N. Engl. J. Med., 2007, vol. 357, pp. 1301–1310.

    Article  CAS  PubMed  Google Scholar 

  • Boden, W.E., High-density lipoprotein cholesterol as an independent risk factor in cardiovascular disease: assessing the data from Framingham to the veterans affairs high-density lipoprotein intervention trial, Am. J. Cardiol., 2000, vol. 86, pp. 19–22.

    Article  Google Scholar 

  • Demina, E.P., Miroshnikova, V.V., Majorov, N.V., Davydenko, V.V., and Schwarzman, A.L., ABCA1 mRNA and protein levels in M-CSF-activated macrophages from patients with arterial stenosis, Cell Tissue Biol., 2013, vol. 7, no. 6, pp. 522–527.

    Article  Google Scholar 

  • Dushkin, M.I., Macrophages and atherosclerosis: pathophysiological and therapeutic aspects, Byull. SO RAMN, 2006, vol. 2, no. 120, pp. 47–55.

    Google Scholar 

  • Escola-Gil, J.C., Cample-Berdiel, L., Palomer, X. Ribas, V., Ordonez-Llanos, J., and Blanco-Vaca, F., Antiatherogenic role of high-density lipoproteins: insights from genetically engineered-mice, Front. Biosci., 2006, vol. 11, pp. 1328–1348.

    Article  CAS  PubMed  Google Scholar 

  • Gelissen, I.C., Harris, M., Rye, K.A., Quinn, C., Brown, A.J., Kockx, M., Cartland, S., Packianathan, M., Kritharides, L., and Jessup, W., ABCA1 and ABCG1 synergize to mediate cholesterol export to ApoA-I, Arterioscler. Thromb. Vasc. Biol., 2006, vol. 26, pp. 534–540.

    Article  CAS  PubMed  Google Scholar 

  • Genvigir, F.D., Rodrigues, A.C., Cerda, A., Arazi, S.S., Willrich, M.A., Oliveira, R., Hirata, M.H., Dorea, E.L., Bernik, M.M., Curi, R., and Hirata, R.D., Effects of lipid-lowering drugs on reverse cholesterol transport gene expressions in peripheral blood mononuclear and HepG2 cells, Pharmacogenomics, 2010, vol. 11, no. 9, pp. 1235–1246.

    Article  CAS  PubMed  Google Scholar 

  • Hovingh, G.K., de, Groot, E., van, der, Steeg, W., Boekholdt, S.M., Hutten, B.A., Kuivenhoven, J.A., and Kastelein, J.J., Inherited disorders of HDL metabolism and atherosclerosis, Curr. Opin. Lipidol., 2005, vol. 16, no. 2, pp. 139–145.

    Article  CAS  PubMed  Google Scholar 

  • Kennedy, M.A., Barrera, G.C., Nakamura, K., Baldan, A., Tarr, P.T., Fishbein, M.C., Frank, J.S., Francone, O., and Edwards, P.A., ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation, Cell. Metab., 2005, vol. 1, pp. 121–131.

    Article  CAS  PubMed  Google Scholar 

  • Lewis, G.F. and Rader, D.J., New insights into the regulation of HDL metabolism and reverse cholesterol transport, Circ. Res., 2005, vol. 96, pp. 1221–1232.

    Article  CAS  PubMed  Google Scholar 

  • Lipovetskii, B.M., Dyslipidemia, Atherosclerosis and Their Relation with Ischemic Heart and Brain Disease, Moscow: Eco-Vector, 2012.

    Google Scholar 

  • Münch, G., Bültmann, A., Li, Z., Holthoff, H.P., Ullrich, J., Wagner, S., and Ungerer, M., Overexpression of ABCG1 protein attenuates arteriosclerosis and endothelial dysfunction in atherosclerotic rabbits, Heart. Int., 2012, vol. 7, pp. e12.

    Article  PubMed Central  PubMed  Google Scholar 

  • Maesh, M., Sendelbach, S., and Lorkowski, S., Selection of reliable reference genes during THP-1 monocyte differentiation into macrophages, BMC Mol. Biol., 2010, vol. 11, pp. 90.

    Google Scholar 

  • Matsuo, M., ATP-binding cassette proteins involved in glucose and lipid homeostasis, Biosci. Biotechnol. Biochem., 2010, vol. 74, no. 5, pp. 899–907.

    Article  CAS  PubMed  Google Scholar 

  • Mauldin, J.P., Nagelin, M.H., Wojcik, A.J., Srinivasan, S., Skaflen, M.D., Ayers, C.R., McNamara, C.A., and Hedrick, C.C., Reduced expression of ABCG1 increases cholesterol accumulation in macrophages of patients with type 2 diabetes, Circulation, 2008, vol. 117, pp. 2785–2792.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Meurs, I., Lammers, B., Zhao, Y., Out, R., Hildebrand, R.B., Hoekstra, M., Van Berkel, T.J.C., and Van Eck, M., The effect of ABCG1 deficiency on atherosclerotic lesion development in LDL receptor knockout mice depends on the stage of atherogenesis, Atherosclerosis, 2012, vol. 221, no. 1, pp. 41–47.

    Article  CAS  PubMed  Google Scholar 

  • Moore, K.J. and Tabas, I., Macrophages in the pathogenesis of atherosclerosis, Cell, 2011, vol. 145, pp. 341–355.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nakanishi, S., Vikstedt, R., Söberlund, S., Lee-Rueckert, M., Hiukka, A., Ehnholm, C., Muilu, M., Metso, J., Naukkarinen, J., Palotie, L., Kovanen, P.T., Jauhiainen, M., and Taskinen, M.R., Serum, but not monocyte macrophage foam cells derived from low HDL-C subjects, displays reduced cholesterol efflux capacity, J. Lipid. Res., 2009, vol. 50, pp. 183–192.

    Article  CAS  PubMed  Google Scholar 

  • Navab, M., Anantharamaiah, G.M., Reddy, S.T., Van, Lenten, B.J., and Fogelman, A.M., HDL as a biomarker, potential therapeutic target, and therapy, Diabetes, 2009, vol. 58, pp. 2711–2717.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sabol, S.L., Brewer, H.B., and Santamarina-Fojo, S., The human ABCG1 gene: identification of LXR response elements that modulate expression in macrophages and liver, J. Lipid. Res., 2005, vol. 46, pp. 2151–2167.

    Article  CAS  PubMed  Google Scholar 

  • Schou, J, Frikke-Schmidt, R, Kardassis, D, Thymiakou, E, Nordestgaard, BG, Grande, P, and Tybjarg-Hansen, A., Genetic variation in ABCG1 and risk of myocardial infarction and ischemic heart disease, Arterioscler. Thromb. Vasc. Biol., 2012, vol. 32, pp. 506–515.

    Article  CAS  PubMed  Google Scholar 

  • Seo, D., Wang, T., Dressman, H., Herderick, E.E., Iversen, E.S., Dong, C., Vata, K., Milano, C.A., Rigat, F., Pittman, J., Nevins, J.R., West, M., and Goldschmidt-Clermont, P.J., Gene expression phenotypes of atherosclerosis, Arterioscler. Thromb. Vasc. Biol., 2004, vol. 24, pp. 1922–1927.

    Article  CAS  PubMed  Google Scholar 

  • Shchelkunova, T.A., Morozov, I.A., Rubtsov, P.M., Samokhodskaya, L.M., Andrianova, I.V., Sobenin, I.A., Orekhov, A.N., and Smirnov, A.N., Changes in levels of gene expression in human aortal intima during atherogenesis, Biochemistry (Moscow), 2013, vol. 78, no. 5, pp. 463–470.

    Article  CAS  Google Scholar 

  • Sinnaeve, P.R., Donahue, M.P., Grass, P., Seo, D., Vonderscher, J.V., Chibout, S.D., Kraus, W.E., Sketch, M., Nelson, C., Ginsburg, G.S., Goldschmidt-Clermont, P.J., and Granger, C.B., Gene expression patterns in peripheral blood correlate with the extent of coronary artery disease, PLoS ONE, 2009, vol. 4, no. 9, p. e7037.

    Article  PubMed Central  PubMed  Google Scholar 

  • Sivapalaratnam, S., Basart, H., Watkins, N.A., Maiwald, S., Rendon, A., Krishnan, U., Sondermeijer, B.M., Creemers, E.E., Pinto-Sietsma, S.J., Hovingh, K., Ouwehand, W.H., Kastelein, J.J., Goodall, A.H., and Trip, M.D., Monocyte gene expression signature of patients with early onset coronary artery disease, PLoS ONE, 2012, vol. 7, p. e32166.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Stein, O. and Stein, Y., Atheroprotective mechanisms of HDL, Atherosclerosis, 1999, vol. 144, pp. 285–301.

    Article  CAS  PubMed  Google Scholar 

  • Tarling, E.J., Expanding roles of ABCG1 and sterol transport, Curr. Opin. Lipidol., 2013, vol. 24, pp. 138–46.

    Article  CAS  PubMed  Google Scholar 

  • Terasaka, N., Yu, S., Yvan-Charvet, L.. Wang, N., Mzhavia, N., Langlois, R., Pagler, T., Welch, C.L., Goldberg, I.J., and Tall, A.R., ABCG1 and HDL protect against endothelial dysfunction in mice fed a high-cholesterol diet, J. Clin. Invest., 2008, vol. 118, pp. 3701–3713.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Waldo, S.W., Li, Y., Buono, C., Zhao, B., Billings, E.M., Chang, J., and Kruth, H.S., Heterogeneity of human macrophages in culture and in atherosclerotic plaques, Am. J. Pathol., 2008, vol. 172, pp. 1112–1126.

    Article  PubMed Central  PubMed  Google Scholar 

  • Westerterp, M., Koetsveld, J., Yu, S., Han, S., Li, R., Goldberg, I.J., Welch, C.L., and Tall, A.R., Increased atherosclerosis in mice with vascular ABCG1 deficiency, Arterioscler. Thromb. Vasc. Biol., 2010, vol. 30, pp. 2103–2105.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wong, J., Quinn, C.M., Gelissen, I.C., Jessup, W., and Brown, A.J., The Effect of statins on ABCA1 and ABCG1 expression in human macrophages is influenced by cellular cholesterol levels and extent of differentiation, Atherosclerosis, 2008, vol. 196, pp. 180–189.

    Article  CAS  PubMed  Google Scholar 

  • Xu, Y., Wang, W., Zhang, L., Qi, L.P., Li, L.Y., Chen, L.F., Fang, Q., Dang, A.M., and Yan, X.W., A Polymorphism in the ABCG1 promoter is functionally associated with coronary artery disease in a chinese han population, Atherosclerosis, 2011, vol. 219, pp. 648–654.

    Article  CAS  PubMed  Google Scholar 

  • Zhou, H., Tan, K.C., Shiu, S.W., and Wong, Y., Determinants of leukocyte adenosine triphosphate binding cassette transporter G1 gene expression in type 2 diabetes mellitus, Metabolism, 2008, vol. 57, pp. 1135–1140.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to V. V. Miroshnikova.

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Original Russian Text © V.V. Miroshnikova, E.P. Demina, N.V. Mayorov, V.V. Davydenko, P.S. Kurjanov, V.N. Vavilov, A.G. Vinogradov, A.D. Denisenko, A.L. Schwarzman, 2014, published in Tsitologiya, 2014, Vol. 56, No. 3, pp. 234–240.

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Miroshnikova, V.V., Demina, E.P., Mayorov, N.V. et al. The expression of ABCG1 transporter gene in peripheral blood mononuclear cells of patients with atherosclerosis. Cell Tiss. Biol. 8, 337–343 (2014). https://doi.org/10.1134/S1990519X14040063

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  • DOI: https://doi.org/10.1134/S1990519X14040063

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