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Proteomic analysis of the triglyceride-rich lipoprotein-laden foam cells

  • Published:
Molecules and Cells

Abstract

In hypertriglyceridaemic individuals, atherosclerogenesis is associated with the increased concentrations of very low density lipoprotein (VLDL) and VLDL-associated remnant particles. In vitro studies have suggested that VLDL induces foam cells formation. To reveal the changes of the proteins expression in the process of foam cells formation induced by VLDL, we performed a proteomic analysis of the foam cells based on the stimulation of differentiated THP-1 cells with VLDL. Using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis, 14 differentially expressed proteins, containing 8 up-regulated proteins and 6 down-regulated proteins were identified. The proteins are involved in energy metabolism, oxidative stress, cell growth, differentiation and apoptosis, such as adipose differentiation-related protein (ADRP), enolase, S100A11, heat shock protein 27 and so on. In addition, the expression of some selected proteins was confirmed by Western blot and RT-PCR analysis. The results suggest that VLDL not only induces lipid accumulation, but also brings about foam cells diverse characteristics by altering the expression of various proteins.

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References

  • Alexander, R.W. (1998). Atheroscleros is as a disease of redox-sensitive genes. Trans. Am. Clin Climatol. Assoc. 109, 129–146.

    PubMed  CAS  Google Scholar 

  • Argmann, C.A., Van Den Diepstraten, C.H., Sawyez, C.G., Edwards, J.Y., Hegele, R.A., Wolfe, B.M., and Huff, M.W. (2001). Transforming growth factor-β1 inhibits macrophage cholesteryl ester accumulation induced by native and oxidized VLDL remnants. Arterioscler. Thromb. Vasc. Biol. 21, 2011–2018.

    Article  PubMed  CAS  Google Scholar 

  • Aronis, A., Madar, Z., and Tirosh, Q. (2005). Mechanism underlying oxidative stress-mediated lipotoxicity: exposure of J774.2 macrophages to triacylglycerols facilitates mitochondrial reactive oxygen species production and cellular necrosis. Free Radic. Biol. Med. 38, 1221–1230.

    Article  PubMed  CAS  Google Scholar 

  • Austin, M.A. (1999). Epidemiology of hypertriglyceridemia and cardiovascular disease. Am. J. Cardiol. 83, 13F–16F.

    Article  PubMed  CAS  Google Scholar 

  • Brasaemle, D.L., Barber, T., Wolins, N., Serrero, G., Blanchette, E.J., and Londos, C. (1997). Adipose differentiation-related protein is an ubiquitouslyexpressed lipid storage droplet associated protein. J. Lipid Res. 38, 2249–2263.

    PubMed  CAS  Google Scholar 

  • Byrne, C.D. (1999). Triglyceride-rich lipoproteins: are links with atherosclerosis mediated by a procoagulant and proinflammatory phenotype? Atherosclerosis 145, 1–15.

    Article  PubMed  CAS  Google Scholar 

  • Carr, T.P., Andresen. C.J., and Rudel, L.L. (1993). Enzymatic determination of triglyceride, free cholesterol, and total cholesterol in tissue lipid extracts. Clin. Biochem. 26, 39–42.

    Article  PubMed  CAS  Google Scholar 

  • Chawla, A., Lee, C.H., Barak, Y., He, W., Rosenfeld, J., Liao, D., Han, J., Kang, H., and Evans, R.M. (2003). PPARδ is a very low-density lipoprotein sensor in macrophages. Proc. Natl. Acad. Sci. USA 100, 1268–1273.

    Article  PubMed  CAS  Google Scholar 

  • Dichtl, W., Nilsson, L., Goncalves, I., Ares, M.P., Banfi, C., Calara, F., Hamsten, A., Eriksson, P., and Nilsson, J. (1999). Very low-density lipoprotein activates nuclear factor-kappaB in endothelial cells. Circ. Res. 84, 1085–1094.

    PubMed  CAS  Google Scholar 

  • Duval, C., Auge, N., Frisach, M.F., Casteilla, L., Salvayre, R., and Negre-Salvayre, A. (2002). Mitochondrial oxidative stress is modulated by oleic acid via an epidermal growth factor receptor-dependent activation of glutathione peroxidase. Biochem. J. 367, 889–894.

    Article  PubMed  CAS  Google Scholar 

  • Evans, A.J., Sawyez, C.G., Wolfe, B.M., Connelly, P.W., Maguire, G.F., and Huff, M.W. (1993). Evidence that cholesteryl ester and triglyceride accumulation in J774.2 macrophages induced by very low density subfractions occurs by different mechanisms. J. Lipid Res. 34, 703–717.

    PubMed  CAS  Google Scholar 

  • Frank, J.S., and Fogelman, A.M. (1989). Ultrastructure of the intima in WHHL and cholesterol-fed rabbit aortas prepared by ultrarapid freezing and freeze-etching. J. Lipid Res. 30, 967–978.

    PubMed  CAS  Google Scholar 

  • Gao, J., and Serrero, G. (1999). Adipose differentiation related protein (ADRP) expressed in transfected COS-7 cells selectively stimulates long chain fatty acid uptake. J. Biol. Chem. 274, 16825–16830.

    Article  PubMed  CAS  Google Scholar 

  • Gordon, D., Reidy, M.A., Benditt, E.P., and Schwartz, S.M. (1990). Cell proliferation in human coronary arteries. Proc. Natl. Acad. Sci. USA 87, 4600–4604.

    Article  PubMed  CAS  Google Scholar 

  • Han, D., Williams, E., and Cadenas, E. (2001). Mitochondrial respiratory chain-dependent generation of superoxide anion and its release into the intermembrane space. Biochem. J. 2001, 353, 411–416.

    Google Scholar 

  • Hokanson, J.E., and Austin, M.A. (1996). Plasma triglyceride level is a risk factor for cardiovascular disease independent of high density lipoprotein cholesterol levels: a meta-analysis of population-based prospective studies. J. Cardiovasc. Risk 3, 213–219.

    Article  PubMed  CAS  Google Scholar 

  • Imamura, M., Inoguchi, T., Ikuyama, S., Taniguchi, S., Kobayashi, K., Nakashima, N., and Nawata, H. (2002). ADRP stimulates lipid accumulation and lipid droplet formation in murine fibroblasts. Am. J. Physiol. Endocrinol. Metab. 283, 775–783.

    Google Scholar 

  • Inada, H., Naka, M., Tanaka, T., Davey, G.E., and Heizmann, C.W. (1999). Human S100A11 exhibits differential steady-state RNA levels in various tissues and a distinct subcellular localization. Biochem. Biophys. Res. Commun. 263, 135–138.

    Article  PubMed  CAS  Google Scholar 

  • Kanamori, T., Takakura, K., Mandai, M., Kariya, M., Fukuhara, K., Sakaguchi, M., Huh, N.H., Saito, K., Sakurai, T., Fujita, J., et al. (2004). Increased expression of calcium-binding protein S100 in human uterine smooth muscle tumours. Mol. Hum. Reprod. 10, 735–742.

    Article  PubMed  CAS  Google Scholar 

  • Larigauderie, G., Cuaz-Perolin, C., Younes, A.B., Furman, C., Lasselin, C., Copin, C., Jaye, M., Fruchart, J.C., and Rouis, M. (2006). Adipophilin increases triglyceride storage in human macrophages by stimulation of biosynthesis and inhibition of b-oxidation. FEBS J. 273, 3498–3351.

    Article  PubMed  CAS  Google Scholar 

  • Martin-Ventura, J.L., Duran, M.C., Blanco-Colio, L.M., Meilhac, O., Leclercq, A., Michel, J.B., Jensen, O.N., Hernandez-Merida, S., Tunon, J., Vivanco, F., et al. (2004). Identification by a differential proteomic approach of heat shock protein 27 as a potential marker of atherosclerosis. Circulation 110, 2216–2219.

    Article  PubMed  CAS  Google Scholar 

  • Martin-Ventura, J.L., Nicolas, V., Houard, X., Blanco-Colio, L.M., Leclercq, A., Egido, J., Vranckx, R., Michel, J.B., and Meilhac, O. (2006). Biological significance of decreased HSP27 in human atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 26, 1337–1343.

    Article  PubMed  CAS  Google Scholar 

  • Memon, A.A., Sorensen, B.S., Meldgaard, P., Fokdal, L., Thykjaer, T., and Nexo, E. (2005). Down-regulation of S100C is associated with bladder cancer progression and poor survival. Clin. Cancer Res. 11, 606–611.

    PubMed  CAS  Google Scholar 

  • Nordestgaard, B.G., Wootton, R., and Lewis, B. (1995). Selective retention of VLDL, IDL, and LDL in the arterial intima of genetically hyperlipidemic rabbits in vivo: Molecular size as a determinant of fractional loss from the intima-inner media. Arterioscler. Thromb. Vasc. Biol. 15, 534–542.

    PubMed  CAS  Google Scholar 

  • Pedrini, M.T., Kranebitter, M., Niederwanger, A., Kaser, S., Engl. J., Debbage, P., Huber, L.A., and Patsch, J.R. (2005). Human triglyceride-rich lipoproteins impair glucose metabolism and insulin signalling in L6 skeletal muscle cells independently of nonesterified fatty acid levels. Diabetologia 48, 756–766.

    Article  PubMed  CAS  Google Scholar 

  • Persson, J., Nilsson, J., and Lindholm, M.W. (2006). Cytokine response to lipoprotein lipid loading in human monocyte-derived macrophages. Lipids Health Dis. 5, 17–24.

    Article  PubMed  Google Scholar 

  • Persson, J., Degerman, E., Nilsson, J., and Lindholm, M.W. (2007). Perilipin and adipophilin expression in lipid loaded macrophages. Biochem. Biophys. Res. Commun. 363, 1020–1026.

    Article  PubMed  CAS  Google Scholar 

  • Rapp, J.H., Lespine, A., Hamilton, R.L., Colyvas, N., Chaumeton, A.H., Tweedie-Hardman. J., and Kane, J.P. (1994). Triglyceride-rich lipoproteins isolated by selected affinity anti-apolipoprotein B immunosorption from human atherosclerotic plaque. Arterioscler Thromb Vasc. Biol. 14, 1767–1774.

    CAS  Google Scholar 

  • Redgrave, T.G., Roberts, D., and West, C.E. (1975). Separation of plasma lipoproteins by density-gradient ultracentrifugation. Anal. Biochem. 65, 42–49.

    Article  PubMed  CAS  Google Scholar 

  • Ricote, M., Valledor, A.F., and Glass, C.K. (2004). Decoding transcriptional programs regulated by PPARs and LXRs in the macrophage: effects on lipid homeostasis, Inflammation, and atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 24, 230–239.

    Article  PubMed  CAS  Google Scholar 

  • Rosenfeld, M.E., and Ross, R. (1990). Macrophage and smooth muscle cell proliferation in atherosclerotic lesions of WHHL and comparably hypercholesterolemic fat-fed rabbits. Arteriosclerosis 10, 680–687.

    PubMed  CAS  Google Scholar 

  • Schmid, G.M., Converset, V., Walter, N., Sennitt, M.V., Leung, K.Y., Byers, H., Ward, M., Hochstrasser, D.F., Cawthorne, M.A., and Sanchez, J.C. (2004). Effect of high-fat diet on the expression of proteins in muscle, adipose tissues, and liver of C57BL/6 mice. Proteomics 4, 2270–2282.

    Article  PubMed  CAS  Google Scholar 

  • Shelness, G.S., and Sellers, J.A. (2001). Very-low-density lipoprotein assembly and secretion. Curr. Opin. Lipidol. 12, 151–157.

    Article  PubMed  CAS  Google Scholar 

  • Stollenwerk, M.M., Schiopu, A., Fredrikson, G.N., Dichtl, W., Nilsson, J., and Ares, M.P. (2005). Very low density lipoprotein potentiates tumor necrosis factor-alpha expression in macrophages. Atherosclerosis. 179, 247–254

    Article  PubMed  CAS  Google Scholar 

  • Sukhanov, S., Higashi, Y., Shai, S.Y., Itabe, H., Ono, K., Parthasarathy, S., and Delafontaine, P. (2006). Novel effect of oxidized low-density lipoprotein: cellular ATP depletion via down-regulation of glyceraldehyde-3-phosphate dehydrogenase. Circ. Res. 99, 191–200.

    Article  PubMed  CAS  Google Scholar 

  • Vanderlaan, P.A., Reardon, C.A., Thisted, R.A., and Getz, G.S. (2009). VLDL best predicts aortic root atherosclerosis in low density lipoprotein receptor deficient mice. J. Lipid Res. 50, 376–385.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Jun Tian.

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Lu, Y., Guo, J., Di, Y. et al. Proteomic analysis of the triglyceride-rich lipoprotein-laden foam cells. Mol Cells 28, 175–181 (2009). https://doi.org/10.1007/s10059-009-0120-1

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  • DOI: https://doi.org/10.1007/s10059-009-0120-1

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