Proatherogenic macrophage activities are targeted by the flavonoid quercetin

Journal of Pharmacology and Experimental Therapeutics

Volumn 343, Issue 2, 2012, Pages 296-306

  Lara Guzman, Oscar J ^a   Tabares Guevara, Jorge H ^a   Leon Varela, Yudy M ^a   Álvarez, Rafael M ^a   Roldan, Miguel ^a   Sierra, Jelver A ^a   Londoño Londõno, Julian A ^a   Ramirez Pineda, Jose R ^a  

^a UNIVERSIDAD DE ANTIOQUIA   (Colombia)

Author keywords

[No Author keywords available]

Indexed keywords

APOLIPOPROTEIN E; CD36 ANTIGEN; CELL PROTEIN; CHOLESTEROL; FAT DROPLET; INFLAMMASOME; INTERLEUKIN 12; INTERLEUKIN 1BETA; INTERLEUKIN 6; LEUCINE RICH REPEAT CONTAINING PROTEIN 3; LIPOPOLYSACCHARIDE; MALONALDEHYDE; MONOCYTE CHEMOTACTIC PROTEIN 1; NUCLEOTIDE BINDING PROTEIN; OXIDIZED LOW DENSITY LIPOPROTEIN; QUERCETIN; REACTIVE OXYGEN METABOLITE; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; AORTA ROOT; ARTICLE; ATHEROMA; ATHEROSCLEROSIS; BONE MARROW; CELL LEVEL; CELL STIMULATION; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; CYTOKINE RELEASE; DRUG MECHANISM; DRUG TARGETING; DYSLIPIDEMIA; FOAM CELL; HUMAN; HYPERLIPOPROTEINEMIA TYPE 3; INFLAMMATORY INFILTRATE; INHIBITION KINETICS; LIPID PEROXIDATION; LIPID STORAGE; MACROPHAGE FUNCTION; MALE; MOUSE; NONHUMAN; OXIDATIVE STRESS; PHAGOCYTOSIS; PRIORITY JOURNAL; PROTECTION; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; T LYMPHOCYTE;

ANIMALS; ANTIGENS, CD36; ANTIOXIDANTS; APOLIPOPROTEINS E; ATHEROSCLEROSIS; CHOLESTEROL; CHOLESTEROL, LDL; CYTOKINES; DIET; ENZYME-LINKED IMMUNOSORBENT ASSAY; FLOW CYTOMETRY; FOAM CELLS; HUMANS; INFLAMMATION; LIPID METABOLISM; MACROPHAGES; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; OXIDATION-REDUCTION; QUERCETIN; REACTIVE OXYGEN SPECIES;

EID: 84867623040     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.112.196147     Document Type: Article

References (60)

1. Amália PM, Possa MN, Augusto MC, and Francisca LS (2007) Quercetin prevents oxidative stress in cirrhotic rats. Dig Dis Sci 52:2616-2621. (Pubitemid 47376649)
2. Auger C, Teissedre PL, Gérain P, Lequeux N, Bornet A, Serisier S, Besançon P, Caporiccio B, Cristol JP, and Rouanet JM (2005) Dietary wine phenolics catechin, quercetin, and resveratrol efficiently protect hypercholesterolemic hamsters against aortic fatty streak accumulation. J Agric Food Chem 53:2015-2021. (Pubitemid 40395767)
3. Bae YS, Lee JH, Choi SH, Kim S, Almazan F, Witztum JL, and Miller YI (2009) Macrophages generate reactive oxygen species in response to minimally oxidized low-density lipoprotein: toll-like receptor 4- and spleen tyrosine kinase-dependent activation of NADPH oxidase 2. Circ Res 104:210-218, 21p following 218.
4. Bhaskar S, Shalini V, and Helen A (2011) Quercetin regulates oxidized LDL induced inflammatory changes in human PBMCs by modulating the TLR-NF-κB signaling pathway. Immunobiology 216:367-373.
5. Boots AW, Haenen GR, and Bast A (2008) Health effects of quercetin: from antioxidant to nutraceutical. Eur J Pharmacol 585:325-337.
6. Chang YC, Lee TS, and Chiang AN (2012) Quercetin enhances ABCA1 expression and cholesterol efflux through a p38-dependent pathway in macrophages. J Lipid Res 53:1840-1850.
7. Chirumbolo S (2010) The role of quercetin, flavonols and flavones in modulating inflammatory cell function. Inflamm Allergy Drug Targets 9:263-285.
8. Choi JS, Bae JY, Kim DS, Li J, Kim JL, Lee YJ, and Kang YH (2010) Dietary compound quercitrin dampens VEGF induction and PPARγ activation in oxidized LDL-exposed murine macrophages: association with scavenger receptor CD36. J Agric Food Chem 58:1333-1341.
9. Cíz M, PavelkováM, GallováL, Králová J, Kubala L, and Lojek A (2008) The influence of wine polyphenols on reactive oxygen and nitrogen species production by murine macrophages RAW 264.7. Physiol Res 57:393-402.
10. Comalada M, Ballester I, Bailón E, Sierra S, Xaus J, Gálvez J, de Medina FS, and Zarzuelo A (2006) Inhibition of pro-inflammatory markers in primary bone marrow-derived mouse macrophages by naturally occurring flavonoids: analysis of the structure-activity relationship. Biochem Pharmacol 72:1010-1021. (Pubitemid 44374465)
11. Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, Abela GS, Franchi L, Nuñez G, Schnurr M, et al. (2010) NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464:1357-1361.
12. Edwards RL, Lyon T, Litwin SE, Rabovsky A, Symons JD, and Jalili T (2007) Quercetin reduces blood pressure in hypertensive subjects. J Nutr 137:2405-2411. (Pubitemid 350058708)
13. Egert S, Bosy-Westphal A, Seiberl J, Kürbitz C, Settler U, Plachta-Danielzik S, Wagner AE, Frank J, Schrezenmeir J, Rimbach G, et al. (2009) Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blinded, placebo-controlled cross-over study. Br J Nutr 102:1065-1074.
14. Ferry DR, Smith A, Malkhandi J, Fyfe DW, deTakats PG, Anderson D, Baker J, and Kerr DJ (1996) Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin Cancer Res 2:659-668. (Pubitemid 26133468)
15. Funk JL, Feingold KR, Moser AH, and Grunfeld C (1993) Lipopolysaccharide stimulation of RAW 264.7 macrophages induces lipid accumulation and foam cell formation. Atherosclerosis 98:67-82. (Pubitemid 23010425)
16. Galkina E and Ley K (2009) Immune and inflammatory mechanisms of atherosclerosis. Annu Rev Immunol 27:165-197.
17. Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352:1685-1695.
18. Hansson GK (2009) Atherosclerosis-an immune disease: The Anitschkov Lecture 2007. Atherosclerosis 202:2-10.
19. Hansson GK and Hermansson A (2011) The immune system in atherosclerosis. Nat Immunol 12:204-212.
20. Harwood M, Danielewska-Nikiel B, Borzelleca JF, Flamm GW, Williams GM, and Lines TC (2007) A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem Toxicol 45:2179-2205. (Pubitemid 47451573)
21. Hayek T, Fuhrman B, Vaya J, Rosenblat M, Belinky P, Coleman R, Elis A, and Aviram M (1997) Reduced progression of atherosclerosis in apolipoprotein E-deficient mice following consumption of red wine, or its polyphenols quercetin or catechin, is associated with reduced susceptibility of LDL to oxidation and aggregation. Arterioscler Thromb Vasc Biol 17:2744-2752. (Pubitemid 28016017)
22. Hertog MG, Feskens EJ, Hollman PC, Katan MB, and Kromhout D (1993) Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 342:1007-1011. (Pubitemid 23314801)
23. Hertog MG, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, Giampaoli S, Jansen A, Menotti A, and Nedeljkovic S (1995) Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med 155:381-386.
24. Hulsmans M and Holvoet P (2010) The vicious circle between oxidative stress and inflammation in atherosclerosis. J Cell Mol Med 14:70-78.
25. Ide N, Keller C, and Weiss N (2006) Aged garlic extract inhibits homocysteine-induced CD36 expression and foam cell formation in human macrophages. J Nutr 136:755S-758S. (Pubitemid 43372206)
26. Jentzsch AM, Bachmann H, Fürst P, and Biesalski HK (1996) Improved analysis of malondialdehyde in human body fluids. Free Radic Biol Med 20:251-256. (Pubitemid 26021882)
27. Juźwiak S, Wójcicki J, Mokrzycki K, Marchlewicz M, Białecka M, Wenda-Rózewicka L, Gawrońska-Szklarz B, and Droździk M (2005) Effect of quercetin on experimental hyperlipidemia and atherosclerosis in rabbits. Pharmacol Rep 57:604-609.
28. Kawai Y, Nishikawa T, Shiba Y, Saito S, Murota K, Shibata N, Kobayashi M, Kanayama M, Uchida K, and Terao J (2008) Macrophage as a target of quercetin glucuronides in human atherosclerotic arteries: implication in the anti-atherosclerotic mechanism of dietary flavonoids. J Biol Chem 283:9424-9434.
29. Kleemann R, Verschuren L, Morrison M, Zadelaar S, van Erk MJ, Wielinga PY, and Kooistra T (2011) Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models. Atherosclerosis 218:44-52.
30. Kobuchi H, Roy S, Sen CK, Nguyen HG, and Packer L (1999) Quercetin inhibits inducible ICAM-1 expression in human endothelial cells through the JNK pathway. Am J Physiol 277:C403-C411. (Pubitemid 29458175)
31. Kostyuk VA, Potapovich AI, Suhan TO, de Luca C, and Korkina LG (2011) Antioxidant and signal modulation properties of plant polyphenols in controlling vascular inflammation. Eur J Pharmacol 658:248-256.
32. Leckey LC, Garige M, Varatharajalu R, Gong M, Nagata T, Spurney CF, and Lakshman RM (2010) Quercetin and ethanol attenuate the progression of atherosclerotic plaques with concomitant up regulation of paraoxonase1 (PON1) gene expression and PON1 activity in LDLR(-/-) mice. Alcohol Clin Exp Res 34:1535-1542.
33. Levitan I, Volkov S, and Subbaiah PV (2010) Oxidized LDL: diversity, patterns of recognition, and pathophysiology. Antioxid Redox Signal 13:39-75.
34. Lian TW, Wang L, Lo YH, Huang IJ, and Wu MJ (2008) Fisetin, morin and myricetin attenuate CD36 expression and oxLDL uptake in U937-derived macrophages. Biochim Biophys Acta 1781:601-609.
35. Loke WM, Proudfoot JM, Hodgson JM, McKinley AJ, Hime N, Magat M, Stocker R, and Croft KD (2010) Specific dietary polyphenols attenuate atherosclerosis in apolipoprotein E-knockout mice by alleviating inflammation and endothelial dysfunction. Arterioscler Thromb Vasc Biol 30:749-757.
36. Lutz MB, Kukutsch N, Ogilvie AL, Rössner S, Koch F, Romani N, and Schuler G (1999) An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J Immunol Methods 223:77-92. (Pubitemid 29096240)
37. Manach C, Williamson G, Morand C, Scalbert A, and Rémésy C (2005) Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 81:230S-242S.
38. Meir KS and Leitersdorf E (2004) Atherosclerosis in the apolipoprotein-E-deficient mouse: a decade of progress. Arterioscler Thromb Vasc Biol 24:1006-1014. (Pubitemid 38737824)
39. Mendoza EE and Burd R (2011) Quercetin as a systemic chemopreventative agent: structural and functional mechanisms. Mini Rev Med Chem 11:1216-1221.
40. Miller YI, Viriyakosol S, Worrall DS, Boullier A, Butler S, and Witztum JL (2005) Toll-like receptor 4-dependent and -independent cytokine secretion induced by minimally oxidized low-density lipoprotein in macrophages. Arterioscler Thromb Vasc Biol 25:1213-1219. (Pubitemid 40776611)
41. Moore KJ and Tabas I (2011) Macrophages in the pathogenesis of atherosclerosis. Cell 145:341-355.
42. Naidu KA and Thippeswamy NB (2002) Inhibition of human low density lipoprotein oxidation by active principles from spices. Mol Cell Biochem 229:19-23.
43. Nam NH (2006) Naturally occurring NF-κB inhibitors. Mini Rev Med Chem 6:945-951.
44. Nicolaou G and Erridge C (2010) Toll-like receptor-dependent lipid body formation in macrophage foam cell formation. Curr Opin Lipidol 21:427-433.
45. Paigen B, Morrow A, Holmes PA, Mitchell D, and Williams RA (1987) Quantitative assessment of atherosclerotic lesions in mice. Atherosclerosis 68:231-240. (Pubitemid 17159775)
46. Panicker SR, Sreenivas P, Babu MS, Karunagaran D, and Kartha CC (2010) Quercetin attenuates monocyte chemoattractant protein-1 gene expression in glucose primed aortic endothelial cells through NF-κB and AP-1. Pharmacol Res 62:328-336.
47. Park JG and Oh GT (2011) The role of peroxidases in the pathogenesis of atherosclerosis. BMB Rep 44:497-505.
48. Perez-Vizcaino F and Duarte J (2010) Flavonols and cardiovascular disease. Mol Aspects Med 31:478-494.
49. Perez-Vizcaino F, Duarte J, and Santos-Buelga C (2012) The flavonoid paradox: conjugation and deconjugation as key steps for the biological activity of flavonoids. J Sci Food Agric 92:1822-1825.
50. Romero M, Jiménez R, Sánchez M, López- Sepúlveda R, Zarzuelo MJ, O'Valle F, Zarzuelo A, Pérez- Vizcaíno F, and Duarte J (2009) Quercetin inhibits vascular superoxide production induced by endothelin-1: Role of NADPH oxidase, uncoupled eNOS and PKC. Atherosclerosis 202:58-67.
51. Russo M, Spagnuolo C, Tedesco I, Bilotto S, and Russo GL (2012) The flavonoid quercetin in disease prevention and therapy: facts and fancies. Biochem Pharmacol 83:6-15.
52. Silverstein RL, Li W, Park YM, and Rahaman SO (2010) Mechanisms of cell signaling by the scavenger receptor CD36: implications in atherosclerosis and thrombosis. Trans Am Clin Climatol Assoc 121:206-220.
53. Stewart CR, Stuart LM, Wilkinson K, van Gils JM, Deng J, Halle A, Rayner KJ, Boyer L, Zhong R, Frazier WA, et al. (2010) CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol 11:155-161.
54. Strowig T, Henao-Mejia J, Elinav E, and Flavell R (2012) Inflammasomes in health and disease. Nature 481:278-286.
55. Tabas I (2010) Macrophage death and defective inflammation resolution in atherosclerosis. Nat Rev Immunol 10:36-46.
56. Tedgui A and Mallat Z (2006) Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev 86:515-581.
57. Tribolo S, Lodi F, Connor C, Suri S, Wilson VG, Taylor MA, Needs PW, Kroon PA, and Hughes DA (2008) Comparative effects of quercetin and its predominant human metabolites on adhesion molecule expression in activated human vascular endothelial cells. Atherosclerosis 197:50-56. (Pubitemid 351273272)
58. Vissiennon C, Nieber K, Kelber O, and Butterweck V (2012) Route of administration determines the anxiolytic activity of the flavonols kaempferol, quercetin and myricetin-are they prodrugs? J Nutr Biochem 23:733-740.
59. Winterbone MS, Tribolo S, Needs PW, Kroon PA, and Hughes DA (2009) Physiologically relevant metabolites of quercetin have no effect on adhesion molecule or chemokine expression in human vascular smooth muscle cells. Atherosclerosis 202:431-438.
60. Xie C, Kang J, Chen JR, Nagarajan S, Badger TM, and Wu X (2011) Phenolic acids are in vivo atheroprotective compounds appearing in the serum of rats after blueberry consumption. J Agric Food Chem 59:10381-10387.