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.
Similar content being viewed by others
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.
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.
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.
Dushkin, M.I., Macrophages and atherosclerosis: pathophysiological and therapeutic aspects, Byull. SO RAMN, 2006, vol. 2, no. 120, pp. 47–55.
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.
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.
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.
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.
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.
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.
Lipovetskii, B.M., Dyslipidemia, Atherosclerosis and Their Relation with Ischemic Heart and Brain Disease, Moscow: Eco-Vector, 2012.
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.
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.
Matsuo, M., ATP-binding cassette proteins involved in glucose and lipid homeostasis, Biosci. Biotechnol. Biochem., 2010, vol. 74, no. 5, pp. 899–907.
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.
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.
Moore, K.J. and Tabas, I., Macrophages in the pathogenesis of atherosclerosis, Cell, 2011, vol. 145, pp. 341–355.
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.
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.
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.
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.
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.
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.
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.
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.
Stein, O. and Stein, Y., Atheroprotective mechanisms of HDL, Atherosclerosis, 1999, vol. 144, pp. 285–301.
Tarling, E.J., Expanding roles of ABCG1 and sterol transport, Curr. Opin. Lipidol., 2013, vol. 24, pp. 138–46.
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.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Corresponding author
Additional information
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.
Rights and permissions
About this article
Cite this article
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
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1990519X14040063