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Methods to Evaluate AMPK Regulation of Macrophage Cholesterol Homeostasis

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AMPK

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1732))

Abstract

Macrophages are a driving force in the development and progression of atherosclerosis, a chronic condition that can lead to cardiovascular disease. In this chapter we describe methods that monitor macrophage cholesterol homeostasis such as cholesterol synthesis, uptake, and efflux, all with the use of AMPK activators and potential genetic models that could help shed light on the role of this metabolic regulator in atherosclerosis and other chronic diseases.

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References

  1. Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, Isasi CR, Jimenez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Mackey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfighi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P, American Heart Association Statistics C, Stroke Statistics S (2017) Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation 135(10):e146–e603. https://doi.org/10.1161/CIR.0000000000000485

    Article  PubMed  PubMed Central  Google Scholar 

  2. Ross R (1999) Atherosclerosis is an inflammatory disease. Am Heart J 138(5 Pt 2):S419–S420

    Article  CAS  PubMed  Google Scholar 

  3. Moore KJ, Sheedy FJ, Fisher EA (2013) Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol 13(10):709–721. https://doi.org/10.1038/nri3520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tabas I (2002) Cholesterol in health and disease. J Clin Invest 110(5):583–590. https://doi.org/10.1172/JCI16381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Tabas I (2010) Macrophage death and defective inflammation resolution in atherosclerosis. Nat Rev Immunol 10(1):36–46. https://doi.org/10.1038/nri2675. nri2675 [pii]

    Article  CAS  PubMed  Google Scholar 

  6. Maxfield FR, Tabas I (2005) Role of cholesterol and lipid organization in disease. Nature 438(7068):612–621. https://doi.org/10.1038/nature04399

    Article  CAS  PubMed  Google Scholar 

  7. Aiello RJ, Brees D, Bourassa PA, Royer L, Lindsey S, Coskran T, Haghpassand M, Francone OL (2002) Increased atherosclerosis in hyperlipidemic mice with inactivation of ABCA1 in macrophages. Arterioscler Thromb Vasc Biol 22(4):630–637

    Article  CAS  PubMed  Google Scholar 

  8. Wang X, Collins HL, Ranalletta M, Fuki IV, Billheimer JT, Rothblat GH, Tall AR, Rader DJ (2007) Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivo. J Clin Invest 117(8):2216–2224. https://doi.org/10.1172/JCI32057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Westerterp M, Murphy AJ, Wang M, Pagler TA, Vengrenyuk Y, Kappus MS, Gorman DJ, Nagareddy PR, Zhu X, Abramowicz S, Parks JS, Welch C, Fisher EA, Wang N, Yvan-Charvet L, Tall AR (2013) Deficiency of ATP-binding cassette transporters A1 and G1 in macrophages increases inflammation and accelerates atherosclerosis in mice. Circ Res 112(11):1456–1465. https://doi.org/10.1161/CIRCRESAHA.113.301086

    Article  CAS  PubMed  Google Scholar 

  10. Khera AV, Cuchel M, de la Llera-Moya M, Rodrigues A, Burke MF, Jafri K, French BC, Phillips JA, Mucksavage ML, Wilensky RL, Mohler ER, Rothblat GH, Rader DJ (2011) Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N Engl J Med 364(2):127–135. https://doi.org/10.1056/NEJMoa1001689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Khera AV, Rader DJ (2013) Cholesterol efflux capacity: full steam ahead or a bump in the road? Arterioscler Thromb Vasc Biol 33(7):1449–1451. https://doi.org/10.1161/ATVBAHA.113.301519

    Article  CAS  PubMed  Google Scholar 

  12. Larach DB, deGoma EM, Rader DJ (2012) Targeting high density lipoproteins in the prevention of cardiovascular disease? Curr Cardiol Rep 14(6):684–691. https://doi.org/10.1007/s11886-012-0317-3

    Article  PubMed  PubMed Central  Google Scholar 

  13. Rader DJ, Tall AR (2012) The not-so-simple HDL story: is it time to revise the HDL cholesterol hypothesis? Nat Med 18(9):1344–1346. https://doi.org/10.1038/nm.2937. nm.2937 [pii]

    Article  CAS  PubMed  Google Scholar 

  14. Galic S, Fullerton MD, Schertzer JD, Sikkema S, Marcinko K, Walkley CR, Izon D, Honeyman J, Chen ZP, van Denderen BJ, Kemp BE, Steinberg GR (2011) Hematopoietic AMPK beta1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity. J Clin Invest 121(12):4903–4915. https://doi.org/10.1172/JCI58577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Fullerton MD, Steinberg GR, Schertzer JD (2013) Immunometabolism of AMPK in insulin resistance and atherosclerosis. Mol Cell Endocrinol 366(2):224–234. https://doi.org/10.1016/j.mce.2012.02.004

    Article  CAS  PubMed  Google Scholar 

  16. O’Neill LA, Hardie DG (2013) Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature 493(7432):346–355. https://doi.org/10.1038/nature11862

    Article  PubMed  Google Scholar 

  17. Day EA, Ford RJ, Steinberg GR (2017) AMPK as a therapeutic target for treating metabolic diseases. Trends Endocrinol Metab. https://doi.org/10.1016/j.tem.2017.05.004

  18. Li D, Wang D, Wang Y, Ling W, Feng X, Xia M (2010) Adenosine monophosphate activated protein kinase induces cholesterol efflux from macrophage-derived foam cells and alleviates atherosclerosis in apolipoprotein E-deficient mice. J Biol Chem 285(43):33499–33509. https://doi.org/10.1074/jbc.M110.159772. M110.159772 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cao Q, Cui X, Wu R, Zha L, Wang X, Parks JS, Yu L, Shi H, Xue B (2016) Myeloid deletion of alpha1AMPK exacerbates atherosclerosis in low density lipoprotein receptor knockout (LDLRKO) mice. Diabetes. https://doi.org/10.2337/db15-0917

  20. Zhang M, Zhu H, Ding Y, Liu Z, Cai Z, Zou MH (2017) AMP-activated protein kinase alpha1 promotes atherogenesis by increasing monocyte-to-macrophage differentiation. J Biol Chem. https://doi.org/10.1074/jbc.M117.779447

  21. Pinkosky SL, Newton RS, Day EA, Ford RJ, Lhotak S, Austin RC, Birch CM, Smith BK, Filippov S, Groot PH, Steinberg GR, Lalwani ND (2016) Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun 7:13457. https://doi.org/10.1038/ncomms13457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wang J, Ma A, Zhao M, Zhu H (2017) AMPK activation reduces the number of atheromata macrophages in ApoE deficient mice. Atherosclerosis 258:97–107. https://doi.org/10.1016/j.atherosclerosis.2017.01.036

    Article  CAS  PubMed  Google Scholar 

  23. Fullerton MD, Ford RJ, McGregor CP, LeBlond ND, Snider SA, Stypa SA, Day EA, Lhotak S, Schertzer JD, Austin RC, Kemp BE, Steinberg GR (2015) Salicylate improves macrophage cholesterol homeostasis via activation of Ampk. J Lipid Res 56(5):1025–1033. https://doi.org/10.1194/jlr.M058875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kim J, Kwak HJ, Cha JY, Jeong YS, Rhee SD, Kim KR, Cheon HG (2014) Metformin suppresses lipopolysaccharide (LPS)-induced inflammatory response in murine macrophages via activating transcription factor-3 (ATF-3) induction. J Biol Chem 289(33):23246–23255. https://doi.org/10.1074/jbc.M114.577908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Jeong HW, Hsu KC, Lee JW, Ham M, Huh JY, Shin HJ, Kim WS, Kim JB (2009) Berberine suppresses proinflammatory responses through AMPK activation in macrophages. Am J Phys Endocrinol Metab 296(4):E955–E964. https://doi.org/10.1152/ajpendo.90599.2008

    Article  CAS  Google Scholar 

  26. Buttari B, Profumo E, Segoni L, D'Arcangelo D, Rossi S, Facchiano F, Saso L, Businaro R, Iuliano L, Rigano R (2014) Resveratrol counteracts inflammation in human M1 and M2 macrophages upon challenge with 7-oxo-cholesterol: potential therapeutic implications in atherosclerosis. Oxidative Med Cell Longev 2014:257543. https://doi.org/10.1155/2014/257543

    Article  Google Scholar 

  27. Tsai JS, Chuang LM, Chen CS, Liang CJ, Chen YL, Chen CY (2014) Troglitazone and Delta2Troglitazone enhance adiponectin expression in monocytes/macrophages through the AMP-activated protein kinase pathway. Mediat Inflamm 2014:726068. https://doi.org/10.1155/2014/726068

    Google Scholar 

  28. Namgaladze D, Snodgrass RG, Angioni C, Grossmann N, Dehne N, Geisslinger G, Brune B (2015) AMP-activated protein kinase suppresses arachidonate 15-lipoxygenase expression in interleukin 4-polarized human macrophages. J Biol Chem 290(40):24484–24494. https://doi.org/10.1074/jbc.M115.678243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lin XL, Liu MH, HJ H, Feng HR, Fan XJ, Zou WW, Pan YQ, Hu XM, Wang Z (2015) Curcumin enhanced cholesterol efflux by upregulating ABCA1 expression through AMPK-SIRT1-LXRalpha signaling in THP-1 macrophage-derived foam cells. DNA Cell Biol 34(9):561–572. https://doi.org/10.1089/dna.2015.2866

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada

    Nicholas D. LeBlond & Morgan D. Fullerton

Authors
  1. Nicholas D. LeBlond
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  2. Morgan D. Fullerton
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Corresponding author

Correspondence to Morgan D. Fullerton .

Editor information

Editors and Affiliations

  1. Department of Pathology CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands

    Dietbert Neumann

  2. Department EMD, Inserm, U1016, Institut Cochin, CNRS, UMR8104, Université Paris Descartes, Paris, France

    Benoit Viollet

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LeBlond, N.D., Fullerton, M.D. (2018). Methods to Evaluate AMPK Regulation of Macrophage Cholesterol Homeostasis. In: Neumann, D., Viollet, B. (eds) AMPK. Methods in Molecular Biology, vol 1732. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7598-3_30

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  • DOI: https://doi.org/10.1007/978-1-4939-7598-3_30

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7597-6

  • Online ISBN: 978-1-4939-7598-3

  • eBook Packages: Springer Protocols

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