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Vitamin E ameliorates ox-LDL-induced foam cells formation through modulating the activities of oxidative stress-induced NF-κB pathway

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Abstract

The role of antioxidant supplementation with vitamin E in the prevention of atherosclerosis has been a topic of considerable recent interest. The relevance of vitamin E for macrophage-derived foam cell formation, a hallmark of atherosclerosis, however, has not been unequivocally resolved. Here, we investigated the effect of Oxidized LDL (ox-LDL) and vitamin E on lipid accumulation and total cholesterol content in U937 macrophages, reactive oxygen species generation and expression of nuclear factor-κB (NF-κB) signaling pathway. The results showed that the mRNA expression and protein levels of P-selectin were evident in U937 macrophages treated with ox-LDL and vitamin E, which indicating that expression of P-selectin is important in macrophage-derived foam cell formation. Moreover, P-selectin changes in ox-LDL-induced foam cell formation can be mediated by vitamin E through activities of nuclear NF-κB activated by serine phosphorylation of NF-κB inhibitor α, suggesting that activation of NF-κB pathway by macrophages may occur. Taken together, these data suggested that vitamin E can prevent ox-LDL-induced foam cell macrophages formation through modulating the activities of oxidative stress-induced NF-κB pathway.

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Abbreviations

DCFH-DA:

20,70-Dichlorofluorescein-diacetate

ECs:

Endothelial cells

FCMs:

Foam cell macrophages

IκBa:

NF-κB inhibitor α

NF-κB:

Nuclear factor-κB

ORO:

Oil red O

ox-LDL:

Oxidized LDL

ROS:

Reactive oxygen species

References

  1. Bousette N, D’Orleans-Juste P, Kiss RS, You Z, Genest J, Al-Ramli W, Qureshi ST, Gramolini A, Behm D, Ohlstein EH, Harrison SM, Douglas SA, Giaid A (2009) Urotensin II receptor knockout mice on an ApoE knockout background fed a high-fat diet exhibit an enhanced hyperlipidemic and atherosclerotic phenotype. Circ Res 105:686–695

    Article  PubMed  CAS  Google Scholar 

  2. Rader DJ, Daugherty A (2008) Translating molecular discoveries into new therapies for atherosclerosis. Nature 451:904–913

    Article  PubMed  CAS  Google Scholar 

  3. Yilmaz O, Celik S, Cay M, Naziroğlu M (1997) Protective role of intraperitoneally administrated vitamin E and selenium on the levels of total lipid, total cholesterol, and fatty acid composition of muscle and liver tissues in rats. J Cell Biochem 64:233–241

    Article  PubMed  CAS  Google Scholar 

  4. Libby P, Ridker PM, Hansson GK (2011) Progress and challenges in translating the biology of atherosclerosis. Nature 473:317–325

    Article  PubMed  CAS  Google Scholar 

  5. Naziroglu M, Brandsch C (2006) Dietary hydrogenated soybean oil affects lipid and vitamin E metabolism in rats. J Nutr Sci Vitaminol (Tokyo) 52:83–88

    Article  CAS  Google Scholar 

  6. Poli G, Sottero B, Gargiulo S, Leonarduzzi G (2009) Cholesterol oxidation products in the vascular remodeling due to atherosclerosis. Mol Aspects Med 30:180–189

    Article  PubMed  CAS  Google Scholar 

  7. Libby P (2002) Inflammation in atherosclerosis. Nature 420:868–874

    Article  PubMed  CAS  Google Scholar 

  8. Wang F, Okamoto Y, Inoki I, Yoshioka K, Du W, Qi X, Takuwa N, Gonda K, Yamamoto Y, Ohkawa R, Nishiuchi T, Sugimoto N, Yatomi Y, Mitsumori K, Asano M, Kinoshita M, Takuwa Y (2010) Sphingosine-1-phosphate receptor-2 deficiency leads to inhibition of macrophage proinflammatory activities and atherosclerosis in apoE-deficient mice. J Clin Invest 120:3979–3995

    Article  PubMed  CAS  Google Scholar 

  9. Naziroğlu M, Simşek M, Simşek H, Aydilek N, Ozcan Z, Atilgan R (2004) The effects of hormone replacement therapy combined with vitamins C and E on antioxidants levels and lipid profiles in postmenopausal women with Type 2 diabetes. Clin Chim Acta 344:63–71

    Article  PubMed  Google Scholar 

  10. Wing LY, Chen YC, Shih YY, Cheng JC, Lin YJ, Jiang MJ (2009) Effects of oral estrogen on aortic ROS-generating and -scavenging enzymes and atherosclerosis in apoE-deficient mice. Exp Biol Med (Maywood) 234:1037–1046

    Article  CAS  Google Scholar 

  11. Hong L, Xie ZZ, Du YH, Tang YB, Tao J, Lv XF, Zhou JG, Guan YY (2011) Alteration of volume-regulated chloride channel during macrophage-derived foam cell formation in atherosclerosis. Atherosclerosis 216:59–66

    Article  PubMed  CAS  Google Scholar 

  12. Saremi A, Arora R (2010) Vitamin E and cardiovascular disease. Am J Ther 17:e56–e65

    Article  PubMed  Google Scholar 

  13. Cabrero A, Cubero M, Llaverías G, Alegret M, Sánchez R, Laguna JC, Vázquez-Carrera M (2005) Leptin down-regulates peroxisome proliferator-activated receptor gamma (PPAR-gamma) mRNA levels in primary human monocyte-derived macrophages. Mol Cell Biochem 275:173–179

    Article  PubMed  CAS  Google Scholar 

  14. Vogel CF, Sciullo E, Matsumura F (2004) Activation of inflammatory mediators and potential role of ah-receptor ligands in foam cell formation. Cardiovasc Toxicol 4:363–373

    Article  PubMed  CAS  Google Scholar 

  15. Zabel U, Schreck R, Baeuerle PA (1991) DNA binding of purified transcription factor NF-kappa B. Affinity, specificity, Zn2+ dependence, and differential half-site recognition. J Biol Chem 266:252–260

    PubMed  CAS  Google Scholar 

  16. Wang L, Yu CJ, Liu W, Cheng LY, Zhang YN (2011) Rosiglitazone protects neuroblastoma cells against advanced glycation end products-induced injury. Acta Pharmacol Sin 32:991–998

    Article  PubMed  Google Scholar 

  17. Liu X, Ntambi JM (2009) Atherosclerosis: keep your macrophages in shape. Nat Med 15:1357–1358

    Article  PubMed  CAS  Google Scholar 

  18. Ferreira V, van Dijk KW, Groen AK, Vos RM, van der Kaa J, Gijbels MJ, Havekes LM, Pannekoek H (2007) Macrophage-specific inhibition of NF-kappaB activation reduces foam-cell formation. Atherosclerosis 192:283–290

    Article  PubMed  CAS  Google Scholar 

  19. Webb NR, Moore KJ (2007) Macrophage-derived foam cells in atherosclerosis lessons from murine models and implications for therapy. Curr Drug Targets 8:1249–1263

    Article  PubMed  CAS  Google Scholar 

  20. Kuhn AM, Tzieply N, Schmidt MV, von Knethen A, Namgaladze D, Yamamoto M, Brüne B (2011) Antioxidant signaling via Nrf2 counteracts lipopolysaccharide-mediated inflammatory responses in foam cell macrophages. Free Radic Biol Med 50:1382–1391

    Article  PubMed  CAS  Google Scholar 

  21. de Winther MP, Kanters E, Kraal G, Hofker MH (2005) Nuclear factor kappaB signaling in atherogenesis. Arterioscler Thromb Vasc Biol 25:904–914

    Article  PubMed  Google Scholar 

  22. Harhaj EW, Dixit VM (2011) Deubiquitinases in the regulation of NF-κB signaling. Cell Res 21:22–39

    Article  PubMed  CAS  Google Scholar 

  23. Xanthoulea S, Curfs DM, Hofker MH, de Winther MP (2005) Nuclear factor kappa B signaling in macrophage function and atherogenesis. Curr Opin Lipidol 16:536–542

    Article  PubMed  CAS  Google Scholar 

  24. Lawrence T, Bebien M, Liu GY, Nizet V, Karin M (2005) IKKalpha limits macrophage NF-kappaB activation and contributes to the resolution of inflammation. Nature 434:1138–1143

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank members of professor Zong-Gui Wu’s laboratory for their helpful discussion and critical reading of the manuscript.

Conflict of interest

The authors have no financial conflicts of interest.

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Authors and Affiliations

  1. Department of Cardiology, Changzheng Hospital, The Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China

    Zhi-Gang Huang, Chun Liang & Zong-Gui Wu

  2. Department of Cardiology, The General Hospital of Jinan Military Region, Jinan, 250031, China

    Shu-Fang Han

Authors
  1. Zhi-Gang Huang
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  2. Chun Liang
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  3. Shu-Fang Han
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  4. Zong-Gui Wu
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Corresponding author

Correspondence to Zong-Gui Wu.

Additional information

Zhi-Gang Huang and Chun Liang contributed equally to this study.

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Huang, ZG., Liang, C., Han, SF. et al. Vitamin E ameliorates ox-LDL-induced foam cells formation through modulating the activities of oxidative stress-induced NF-κB pathway. Mol Cell Biochem 363, 11–19 (2012). https://doi.org/10.1007/s11010-011-1153-2

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  • DOI: https://doi.org/10.1007/s11010-011-1153-2

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