Roles of xenobiotic receptors in vascular pathophysiology

Circulation Journal

Volumn 78, Issue 7, 2014, Pages 1520-1530

  Xiao, Lei ^a   Zhang, Zihui ^a   Luo, Xiaoqin ^a  

^a XI'AN JIAOTONG UNIVERSITY   (China)

Author keywords

Aryl hydrocarbon receptor; Constitutive androstane receptor; Pregnane X receptor; Vascular diseases

Indexed keywords

1, 4 BIS (3, 5 DICHLORO 2 PYRIDYLOXY) BENZENE; 16ALPHA CYANOPREGNENOLONE; 2, 3, 7, 8 TETRACHLORODIBENZO PARA DIOXIN; ALDEHYDE DEHYDROGENASE; ANDROSTANE DERIVATIVE; AROMATIC HYDROCARBON RECEPTOR; CAFESTOL; CHLORPROMAZINE; CLOTRIMAZOLE; CONSTITUTIVE ANDROSTANE RECEPTOR; COUMESTROL; GUGGULSTERONE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; HYPERFORIN; ISOFLAVONE; LIGAND; LITHOCHOLIC ACID; METYRAPONE; MIFEPRISTONE; PACLITAXEL; PHENOBARBITAL; PREGNANE X RECEPTOR; PREGNENOLONE; PROGESTERONE; RETINOIC ACID; RIFAMPICIN; RITONAVIR; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; XENOBIOTIC AGENT; CELL RECEPTOR; STEROID RECEPTOR;

ATHEROSCLEROSIS; BILE ACID METABOLISM; DRUG METABOLISM; GENE; GLUCOSE HOMEOSTASIS; HUMAN; HYPERTENSION; INFLAMMATION; LIPID HOMEOSTASIS; NONHUMAN; PATHOPHYSIOLOGY; PROTEIN FUNCTION; REVIEW; VASCULAR DISEASE; ANIMAL; GENE EXPRESSION REGULATION; HYPERLIPIDEMIA; METABOLISM; PATHOLOGY;

ANIMALS; ATHEROSCLEROSIS; GENE EXPRESSION REGULATION; HUMANS; HYPERLIPIDEMIAS; HYPERTENSION; RECEPTORS, ARYL HYDROCARBON; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECEPTORS, STEROID;

EID: 84903201801     PISSN: 13469843     EISSN: 13474820     Source Type: Journal    
DOI: 10.1253/circj.CJ-14-0343     Document Type: Review

References (142)

1. Gao J, Xie W. Targeting xenobiotic receptors PXR and CAR for metabolic diseases. Trends Pharmacol Sci 2012; 33: 552-558.
2. Fuhr U. Induction of drug metabolising enzymes: Pharmacokinetic and toxicological consequences in humans. Clin Pharmacokinet 2000; 38: 493-504.
3. Dixit SG, Tirona RG, Kim RB. Beyond CAR and PXR. Curr Drug Metab 2005; 6: 385-397.
4. Chang TK, Waxman DJ. Synthetic drugs and natural products as modulators of constitutive androstane receptor (CAR) and pregnane X receptor (PXR). Drug Metab Rev 2006; 38: 51-73.
5. Moreau A, Vilarem MJ, Maurel P, Pascussi JM. Xenoreceptors CAR and PXR activation and consequences on lipid metabolism, glucose homeostasis, and inflammatory response. Mol Pharm 2008; 5: 35-41.
6. Francis GA, Fayard E, PiCARd F, Auwerx J. Nuclear receptors and the control of metabolism. Annu Rev Physiol 2003; 65: 261-311.
7. Rendic S, Di Carlo FJ. Human cytochrome p450 enzymes: A status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab Rev 1997; 29: 413-580.
8. Oesch F, Herrero ME, Hengstler JG, Lohmann M, Arand M. Metabolic detoxification: Implications for thresholds. Toxicol Pathol 2000; 28: 382-387.
9. Handschin C, Meyer UA. Regulatory network of lipid-sensing nuclear receptors: Roles for CAR, PXR, LXR, and FXR. Arch Biochem Biophys 2005; 433: 387-396.
10. Willson TM, Kliewer SA. PXR, CAR and drug metabolism. Nat Rev Drug Discov 2002; 1: 259-266.
11. McCarver DG, Hines RN. The ontogeny of human drug-metabolizing enzymes: Phase II conjugation enzymes and regulatory mechanisms. J Pharmacol Exp Ther 2002; 300: 361-366.
12. Tolson AH, Wang H. Regulation of drug-metabolizing enzymes by xenobiotic receptors: PXR and CAR. Adv Drug Deliv Rev 2010; 62: 1238-1249.
13. Hao N, Whitelaw ML. The emerging roles of AHR in physiology and immunity. Biochem Pharmacol 2013; 86: 561-570.
14. Hoffman EC, Reyes H, Chu FF, Sander F, Conley LH, Brooks BA, et al. Cloning of a factor required for activity of the Ah (dioxin) receptor. Science 1991; 252: 954-958.
15. Fujisawa-Sehara A, Sogawa K, Yamane M, Fujii-Kuriyama Y. Characterization of xenobiotic responsive elements upstream from the drug-metabolizing cytochrome p-450c gene: A similarity to glucocorticoid regulatory elements. Nucleic Acids Res 1987; 15: 4179-4191.
16. Sherr DH. Another important biological function for the aryl hydrocarbon receptor. Arterioscler Thromb Vasc Biol 2011; 31: 1247-1248.
17. Ihunnah CA, Jiang M, Xie W. Nuclear receptor PXR, transcriptional circuits and metabolic relevance. Biochim Biophys Acta 2011; 1812: 956-963.
18. Kodama S, Koike C, Negishi M, Yamamoto Y. Nuclear receptors CAR and PXR cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes. Mol Cell Biol 2004; 24: 7931-7940.
19. Korashy HM, El-Kadi AO. The role of aryl hydrocarbon receptor in the pathogenesis of cardiovascular diseases. Drug Metab Rev 2006; 38: 411-450.
20. Bertilsson G, Heidrich J, Svensson K, Asman M, Jendeberg L, Sydow-Backman M, et al. Identification of a human nuclear receptor defines a new signaling pathway for CYP3a induction. Proc Natl Acad Sci USA 1998; 95: 12208-12213.
21. Hustert E, Zibat A, Presecan-Siedel E, Eiselt R, Mueller R, Fuss C, et al. Natural protein variants of pregnane X receptor with altered transactivation activity toward CYP3a4. Drug Metab Dispos 2001; 29: 1454-1459.
22. Kliewer SA, Goodwin B, Willson TM. The nuclear pregnane X receptor: A key regulator of xenobiotic metabolism. Endocr Rev 2002; 23: 687-702.
23. Baes M, Gulick T, Choi HS, Martinoli MG, Simha D, Moore DD. A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements. Mol Cell Biol 1994; 14: 1544-1552.
24. Alexander DL, Eltom SE, Jefcoate CR. Ah receptor regulation of CYP1b1 expression in primary mouse embryo-derived cells. Cancer Res 1997; 57: 4498-4506.
25. Hankinson O. Role of coactivators in transcriptional activation by the aryl hydrocarbon receptor. Arch Biochem Biophys 2005; 433: 379-386.
26. Nakata K, Tanaka Y, Nakano T, Adachi T, Tanaka H, Kaminuma T, et al. Nuclear receptor-mediated transcriptional regulation in phase I, II, and III xenobiotic metabolizing systems. Drug Metab Pharmacokinet 2006; 21: 437-457.
27. Moore LB, Parks DJ, Jones SA, Bledsoe RK, Consler TG, Stimmel JB, et al. Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands. J Biol Chem 2000; 275: 15122-15127.
28. Howe K, Sanat F, Thumser AE, Coleman T, Plant N. The statin class of HMG-CoA reductase inhibitors demonstrate differential activation of the nuclear receptors PXR, CAR and FXR, as well as their downstream target genes. Xenobiotica 2011; 41: 519-529.
29. Synold TW, Dussault I, Forman BM. The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat Med 2001; 7: 584-590.
30. Kobayashi K, Yamanaka Y, Iwazaki N, Nakajo I, Hosokawa M, Negishi M, et al. Identification of HMG-CoA reductase inhibitors as activators for human, mouse and rat constitutive androstane receptor. Drug Metab Dispos 2005; 33: 924-929.
31. Poland RE, Rubin RT. Radioimmunoassay of haloperidol in human serum: Correlation of serum haloperidol with serum prolactin. Life Sci 1981; 29: 1837-1845.
32. Tontonoz P, Mangelsdorf DJ. Liver X receptor signaling pathways in cardiovascular disease. Mol Endocrinol 2003; 17: 985-993.
33. Jacobs MN, Dickins M, Lewis DF. Homology modelling of the nuclear receptors: Human oestrogen receptorbeta (HERbeta), the human pregnane-X-receptor (PXR), the aH receptor (AhR) and the constitutive androstane receptor (CAR) ligand binding domains from the human oestrogen receptor alpha (HERalpha) crystal structure, and the human peroxisome proliferator activated receptor alpha (PPARalpha) ligand binding domain from the human PPARgamma crystal structure. J Steroid Biochem Mol Biol 2003; 84: 117-132.
34. Xie W, Barwick JL, Simon CM, Pierce AM, Safe S, Blumberg B, et al. Reciprocal activation of xenobiotic response genes by nuclear receptors SXR/PXR and CAR. Genes Dev 2000; 14: 3014-3023.
35. Wei P, Zhang J, Dowhan DH, Han Y, Moore DD. Specific and overlapping functions of the nuclear hormone receptors CAR and PXR in xenobiotic response. Pharmacogenomics J 2002; 2: 117-126.
36. Moore JT, Moore LB, Maglich JM, Kliewer SA. Functional and structural comparison of PXR and CAR. Biochim Biophys Acta 2003; 1619: 235-238.
37. Forman BM, Tzameli I, Choi HS, Chen J, Simha D, Seol W, et al. Androstane metabolites bind to and deactivate the nuclear receptor CAR-beta. Nature 1998; 395: 612-615.
38. Kakizaki S, Yamazaki Y, Takizawa D, Negishi M. New insights on the xenobiotic-sensing nuclear receptors in liver diseases; CAR and PXR. Curr Drug Metab 2008; 9: 614-621.
39. Qatanani M, Zhang J, Moore DD. Role of the constitutive androstane receptor in xenobiotic-induced thyroid hormone metabolism. Endocrinology 2005; 146: 995-1002.
40. Ma X, Idle JR, Gonzalez FJ. The pregnane X receptor: From bench to bedside. Expert Opin Drug Metab Toxicol 2008; 4: 895-908.
41. Lichti-Kaiser K, Brobst D, Xu C, Staudinger JL. A systematic analysis of predicted phosphorylation sites within the human pregnane X receptor protein. J Pharmacol Exp Ther 2009; 331: 65-76.
42. Staudinger JL, Xu C, Biswas A, Mani S. Post-translational modification of pregnane X receptor. Pharmacol Res 2011; 64: 4-10.
43. Biswas A, Pasquel D, Tyagi RK, Mani S. Acetylation of pregnane X receptor protein determines selective function independent of ligand activation. Biochem Biophys Res Commun 2011; 406: 371-376.
44. Hosseinpour F, Moore R, Negishi M, Sueyoshi T. Serine 202 regulates the nuclear translocation of constitutive active/androstane receptor. Mol Pharmacol 2006; 69: 1095-1102.
45. Denison MS, Pandini A, Nagy SR, Baldwin EP, Bonati L. Ligand binding and activation of the Ah receptor. Chem Biol Interact 2002; 141: 3-24.
46. Denison MS, Nagy SR. Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals. Annu Rev Pharmacol Toxicol 2003; 43: 309-334.
47. Adachi J, Mori Y, Matsui S, Takigami H, Fujino J, Kitagawa H, et al. Indirubin and indigo are potent aryl hydrocarbon receptor ligands present in human urine. J Biol Chem 2001; 276: 31475-31478.
48. Sinal CJ, Bend JR. Aryl hydrocarbon receptor-dependent induction of CYP1a1 by bilirubin in mouse hepatoma HEPA 1c1c7 cells. Mol Pharmacol 1997; 52: 590-599.
49. Seidel SD, Winters GM, Rogers WJ, Ziccardi MH, Li V, Keser B, et al. Activation of the Ah receptor signaling pathway by prostaglandins. J Biochem Mol Toxicol 2001; 15: 187-196.
50. Zhang N. The role of endogenous aryl hydrocarbon receptor signaling in cardiovascular physiology. J Cardiovasc Dis Res 2011; 2: 91-95.
51. Boisvert WA, Santiago R, Curtiss LK, Terkeltaub RA. A leukocyte homologue of the IL-8 receptor CXCR-2 mediates the accumulation of macrophages in atherosclerotic lesions of LDL receptordeficient mice. J Clin Invest 1998; 101: 353-363.
52. Swales KE, Bishop-Bailey D. The potential use of the pregnane X receptor in cardiovascular therapy. Expert Rev Cardiovasc Ther 2012; 10: 1079-1082.
53. Wang X, Fang X, Zhou J, Chen Z, Zhao B, Xiao L, et al. Shear stress activation of nuclear receptor PXR in endothelial detoxification. Proc Natl Acad Sci USA 2013; 110: 13174-13179.
54. Swales KE, Moore R, Truss NJ, Tucker A, Warner TD, Negishi M, et al. Pregnane X receptor regulates drug metabolism and transport in the vasculature and protects from oxidative stress. Cardiovasc Res 2012; 93: 674-681.
55. Zhou J, Zhai Y, Mu Y, Gong H, Uppal H, Toma D, et al. A novel pregnane X receptor-mediated and sterol regulatory element-binding protein-independent lipogenic pathway. J Biol Chem 2006; 281: 15013-15020.
56. Spencer M, Yao-Borengasser A, Unal R, Rasouli N, Gurley CM, Zhu B, et al. Adipose tissue macrophages in insulin-resistant subjects are associated with collagen VI and fibrosis and demonstrate alternative activation. Am J Physiol Endocrinol Metab 2010; 299: E1016-E1027, doi:10.1152/ajpendo.00329.2010.
57. Hu G, Xu C, Staudinger JL. Pregnane X receptor is SUMOylated to repress the inflammatory response. J Pharmacol Exp Ther 2010; 335: 342-350.
58. Wallace K, Cowie DE, Konstantinou DK, Hill SJ, Tjelle TE, Axon A, et al. The PXR is a drug target for chronic inflammatory liver disease. J Steroid Biochem Mol Biol 2010; 120: 137-148.
59. Cheng J, Shah YM, Ma X, Pang X, Tanaka T, Kodama T, et al. Therapeutic role of rifaximin in inflammatory bowel disease: Clinical implication of human pregnane X receptor activation. J Pharmacol Exp Ther 2010; 335: 32-41.
60. Ghose R, Guo T, Vallejo JG, Gandhi A. Differential role of tollinterleukin 1 receptor domain-containing adaptor protein in toll-like receptor 2-mediated regulation of gene expression of hepatic cytokines and drug-metabolizing enzymes. Drug Metab Dispos 2011; 39: 874-881.
61. Ghose R, Omoluabi O, Gandhi A, Shah P, Strohacker K, Carpenter KC, et al. Role of high-fat diet in regulation of gene expression of drug metabolizing enzymes and transporters. Life Sci 2011; 89: 57-64.
62. Zhou C, Tabb MM, Nelson EL, Grun F, Verma S, Sadatrafiei A, et al. Mutual repression between steroid and xenobiotic receptor and NF-kappaB signaling pathways links xenobiotic metabolism and inflammation. J Clin Invest 2006; 116: 2280-2289.
63. Hofmann AF, Borgstroem B. The intraluminal phase of fat digestion in man: The lipid content of the micellar and oil phases of intestinal content obtained during fat digestion and absorption. J Clin Invest 1964; 43: 247-257.
64. Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: Meta-analysis of individual data from 27 randomised trials. Lancet 2012; 380: 581-590.
65. Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, MacKenzie KI, LaTour A, et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci USA 2001; 98: 3369-3374.
66. Xie W, Radominska-Pandya A, Shi Y, Simon CM, Nelson MC, Ong ES, et al. An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc Natl Acad Sci USA 2001; 98: 3375-3380.
67. Uppal H, Toma D, Saini SP, Ren S, Jones TJ, Xie W. Combined loss of orphan receptors PXR and CAR heightens sensitivity to toxic bile acids in mice. Hepatology 2005; 41: 168-176.
68. Goodwin B, Gauthier KC, Umetani M, Watson MA, Lochansky MI, Collins JL, et al. Identification of bile acid precursors as endogenous ligands for the nuclear xenobiotic pregnane X receptor. Proc Natl Acad Sci USA 2003; 100: 223-228.
69. Zhou C, Verma S, Blumberg B. The steroid and xenobiotic receptor (SXR), beyond xenobiotic metabolism. Nucl Recept Signal 2009; 7: e001, doi:10.1621/nrs.07001.
70. Cheng X, Maher J, Dieter MZ, Klaassen CD. Regulation of mouse organic anion-transporting polypeptides (OATPs) in liver by prototypical microsomal enzyme inducers that activate distinct transcription factor pathways. Drug Metab Dispos 2005; 33: 1276-1282.
71. Maher JM, Cheng X, Slitt AL, Dieter MZ, Klaassen CD. Induction of the multidrug resistance-associated protein family of transporters by chemical activators of receptor-mediated pathways in mouse liver. Drug Metab Dispos 2005; 33: 956-962.
72. Petrick JS, Klaassen CD. Importance of hepatic induction of constitutive androstane receptor and other transcription factors that regulate xenobiotic metabolism and transport. Drug Metab Dispos 2007; 35: 1806-1815.
73. Kiuchi Y, Suzuki H, Hirohashi T, Tyson CA, Sugiyama Y. CDNA cloning and inducible expression of human multidrug resistance associated protein 3 (MRP3). FEBS Lett 1998; 433: 149-152.
74. Jigorel E, Le Vee M, Boursier-Neyret C, Parmentier Y, Fardel O. Differential regulation of sinusoidal and canalicular hepatic drug transporter expression by xenobiotics activating drug-sensing receptors in primary human hepatocytes. Drug Metab Dispos 2006; 34: 1756-1763.
75. Olinga P, Elferink MG, Draaisma AL, Merema MT, Castell JV, Perez G, et al. Coordinated induction of drug transporters and phase I and II metabolism in human liver slices. Eur J Pharm Sci 2008; 33: 380-389.
76. Richert L, Tuschl G, Abadie C, Blanchard N, Pekthong D, Mantion G, et al. Use of mRNA expression to detect the induction of drug metabolising enzymes in rat and human hepatocytes. Toxicol Appl Pharmacol 2009; 235: 86-96.
77. Kliewer SA, Moore JT, Wade L, Staudinger JL, Watson MA, Jones SA, et al. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell 1998; 92: 73-82.
78. Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM, Luk A, et al. Identification of a nuclear receptor for bile acids. Science 1999; 284: 1362-1365.
79. Kassam A, Winrow CJ, Fernandez-Rachubinski F, Capone JP, Rachubinski RA. The peroxisome proliferator response element of the gene encoding the peroxisomal beta-oxidation enzyme enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase is a target for constitutive androstane receptor beta/9-cis-retinoic acid receptormediated transactivation. J Biol Chem 2000; 275: 4345-4350.
80. Ueda A, Hamadeh HK, Webb HK, Yamamoto Y, Sueyoshi T, Afshari CA, et al. Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital. Mol Pharmacol 2002; 61: 1-6.
81. Sui Y, Xu J, Rios-Pilier J, Zhou C. Deficiency of PXR decreases atherosclerosis in ApoE-deficient mice. J Lipid Res 2011; 52: 1652-1659.
82. Gao J, Xie W. Pregnane X receptor and constitutive androstane receptor at the crossroads of drug metabolism and energy metabolism. Drug Metab Dispos 2010; 38: 2091-2095.
83. Roth A, Looser R, Kaufmann M, Blattler SM, Rencurel F, Huang W, et al. Regulatory cross-talk between drug metabolism and lipid homeostasis: Constitutive androstane receptor and pregnane X receptor increase Insig-1 expression. Mol Pharmacol 2008; 73: 1282-1289.
84. Hamlat N, Forcheron F, Negazzi S, del Carmine P, Feugier P, Bricca G, et al. Lipogenesis in arterial wall and vascular smooth muscular cells: Regulation and abnormalities in insulin-resistance. Cardiovasc Diabetol 2009; 8: 64.
85. Lahtela JT, Arranto AJ, Sotaniemi EA. Enzyme inducers improve insulin sensitivity in non-insulin-dependent diabetic subjects. Diabetes 1985; 34: 911-916.
86. Miao J, Fang S, Bae Y, Kemper JK. Functional inhibitory cross-talk between constitutive androstane receptor and hepatic nuclear factor-4 in hepatic lipid/glucose metabolism is mediated by competition for binding to the DR1 motif and to the common coactivators, GRIP-1 and PGC-1alpha. J Biol Chem 2006; 281: 14537-14546.
87. Carver LA, Hogenesch JB, Bradfield CA. Tissue specific expression of the rat Ah-receptor and ARNT mRNAs. Nucleic Acids Res 1994; 22: 3038-3044.
88. Mehrabi MR, Steiner GE, Dellinger C, Kofler A, Schaufler K, Tamaddon F, et al. The arylhydrocarbon receptor (AhR), but not the AhR-nuclear translocator (ARNT), is increased in hearts of patients with cardiomyopathy. Virchows Arch 2002; 441: 481-489.
89. Takahashi Y, Nakayama K, Shimojima T, Itoh S, Kamataki T. Expression of aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear translocator (ARNT) in adult rabbits known to be non-responsive to cytochrome p-450 1a1 (CYP1a1) inducers. Eur J Biochem 1996; 242: 512-518.
90. Hankinson O. Dominant and recessive aryl hydrocarbon hydroxylase-deficient mutants of mouse hepatoma line, HEPA-1, and assignment of recessive mutants to three complementation groups. Somatic Cell Genet 1983; 9: 497-514.
91. Poland AP, Glover E, Robinson JR, Nebert DW. Genetic expression of aryl hydrocarbon hydroxylase activity: Induction of monooxygenase activities and cytochrome p1-450 formation by 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice genetically "nonresponsive" to other aromatic hydrocarbons. J Biol Chem 1974; 249: 5599-5606.
92. Nebert DW, Gielen JE. Genetic regulation of aryl hydrocarbon hydroxylase induction in the mouse. Fed Proc 1972; 31: 1315-1325.
93. Vogel CF, Sciullo E, Matsumura F. Activation of inflammatory mediators and potential role of Ah-receptor ligands in foam cell formation. Cardiovasc Toxicol 2004; 4: 363-373.
94. Liu S, Abdelrahim M, Khan S, Ariazi E, Jordan VC, Safe S. Aryl hydrocarbon receptor agonists directly activate estrogen receptor alpha in MCF-7 breast cancer cells. Biol Chem 2006; 387: 1209-1213.
95. Ohtake F, Takeyama K, Matsumoto T, Kitagawa H, Yamamoto Y, Nohara K, et al. Modulation of oestrogen receptor signalling by association with the activated dioxin receptor. Nature 2003; 423: 545-550.
96. Schlezinger JJ, Liu D, Farago M, Seldin DC, Belguise K, Sonenshein GE, et al. A role for the aryl hydrocarbon receptor in mammary gland tumorigenesis. Biol Chem 2006; 387: 1175-1187.
97. Zhang S, Lei P, Liu X, Li X, Walker K, Kotha L, et al. The aryl hydrocarbon receptor as a target for estrogen receptor-negative breast cancer chemotherapy. Endocr Relat Cancer 2009; 16: 835-844.
98. Vogel CF, Sciullo E, Wong P, Kuzmicky P, Kado N, Matsumura F. Induction of proinflammatory cytokines and C-reactive protein in human macrophage cell line U937 exposed to air pollution particulates. Environ Health Perspect 2005; 113: 1536-1541.
99. Pelclova D, Fenclova Z, Preiss J, Prochazka B, Spacil J, Dubska Z, et al. Lipid metabolism and neuropsychological follow-up study of workers exposed to 2,3,7,8-tetrachlordibenzo-p-dioxin. Int Arch Occup Environ Health 2002; 75(Suppl): S60-S66.
100. Mathiesen M, Pedersen EK, Bjorseth O, Egeberg KW, Syversen T. Heating of indoor dust causes reduction in its ability to stimulate release of IL-8 and TNFalpha in vitro compared to non-heated dust. Indoor Air 2004; 14: 226-234.
101. Wu D, Nishimura N, Kuo V, Fiehn O, Shahbaz S, Van Winkle L, et al. Activation of aryl hydrocarbon receptor induces vascular inflammation and promotes atherosclerosis in apolipoprotein E-/-mice. Arterioscler Thromb Vasc Biol 2011; 31: 1260-1267.
102. Schlezinger JJ, Stegeman JJ. Dose and inducer-dependent induction of cytochrome p450 1a in endothelia of the eel, including in the swimbladder rete mirabile, a model microvascular structure. Drug Metab Dispos 2000; 28: 701-708.
103. Wang N, Yin R, Liu Y, Mao G, Xi F. Role of peroxisome proliferator-activated receptor-gamma in atherosclerosis: An update. Circ J 2011; 75: 528-535.
104. Cheang WS, Fang X, Tian XY. Pleiotropic effects of peroxisome proliferator-activated receptor gamma and delta in vascular diseases. Circ J 2013; 77: 2664-2671.
105. Oesterling E, Toborek M, Hennig B. Benzo[a]pyrene induces intercellular adhesion molecule-1 through a caveolae and aryl hydrocarbon receptor mediated pathway. Toxicol Appl Pharmacol 2008; 232: 309-316.
106. Watanabe I, Tatebe J, Namba S, Koizumi M, Yamazaki J, Morita T. Activation of aryl hydrocarbon receptor mediates indoxyl sulfateinduced monocyte chemoattractant protein-1 expression in human umbilical vein endothelial cells. Circ J 2013; 77: 224-230.
107. Coogan PF, White LF, Jerrett M, Brook RD, Su JG, Seto E, et al. Air pollution and incidence of hypertension and diabetes mellitus in black women living in Los Angeles. Circulation 2012; 125: 767-772.
108. Lund AK, Agbor LN, Zhang N, Baker A, Zhao H, Fink GD, et al. Loss of the aryl hydrocarbon receptor induces hypoxemia, endothelin-1, and systemic hypertension at modest altitude. Hypertension 2008; 51: 803-809.
109. Kopf PG, Huwe JK, Walker MK. Hypertension, cardiac hypertrophy, and impaired vascular relaxation induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin are associated with increased superoxide. Cardiovasc Toxicol 2008; 8: 181-193.
110. Kang HK, Dalager NA, Needham LL, Patterson DG Jr, Lees PS, Yates K, et al. Health status of Army Chemical Corps Vietnam veterans who sprayed defoliant in Vietnam. Am J Ind Med 2006; 49: 875-884.
111. Kim JS, Lim HS, Cho SI, Cheong HK, Lim MK. Impact of agent orange exposure among Korean Vietnam veterans. Ind Health 2003; 41: 149-157.
112. Dalton TP, Kerzee JK, Wang B, Miller M, Dieter MZ, Lorenz JN, et al. Dioxin exposure is an environmental risk factor for ischemic heart disease. Cardiovasc Toxicol 2001; 1: 285-298.
113. Pesatori AC, Zocchetti C, Guercilena S, Consonni D, Turrini D, Bertazzi PA. Dioxin exposure and non-malignant health effects: A mortality study. Occup Environ Med 1998; 55: 126-131.
114. Lund AK, Goens MB, Kanagy NL, Walker MK. Cardiac hypertrophy in aryl hydrocarbon receptor null mice is correlated with elevated angiotensin II, endothelin-1, and mean arterial blood pressure. Toxicol Appl Pharmacol 2003; 193: 177-187.
115. Agbor LN, Elased KM, Walker MK. Endothelial cell-specific aryl hydrocarbon receptor knockout mice exhibit hypotension mediated, in part, by an attenuated angiotensin II responsiveness. Biochem Pharmacol 2011; 82: 514-523.
116. Kopf PG, Walker MK. 2,3,7,8-tetrachlorodibenzo-p-dioxin increases reactive oxygen species production in human endothelial cells via induction of cytochrome p4501a1. Toxicol Appl Pharmacol 2010; 245: 91-99.
117. Kimura A, Naka T, Nohara K, Fujii-Kuriyama Y, Kishimoto T. Aryl hydrocarbon receptor regulates STAT1 activation and participates in the development of Th17 cells. Proc Natl Acad Sci USA 2008; 105: 9721-9726.
118. Guzik TJ, Hoch NE, Brown KA, McCann LA, Rahman A, Dikalov S, et al. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med 2007; 204: 2449-2460.
119. Mani S, Dou W, Redinbo MR. PXR antagonists and implication in drug metabolism. Drug Metab Rev 2013; 45: 60-72.
120. Chen T. Overcoming drug resistance by regulating nuclear receptors. Adv Drug Deliv Rev 2010; 62: 1257-1264.
121. Wang XL, Raveendran M, Wang J. Genetic influence on cigaretteinduced cardiovascular disease. Prog Cardiovasc Dis 2003; 45: 361-382.
122. Zordoky BN, El-Kadi AO. Effect of cytochrome p450 polymorphism on arachidonic acid metabolism and their impact on cardiovascular diseases. Pharmacol Ther 2010; 125: 446-463.
123. Bozina N, Bradamante V, Lovric M. Genetic polymorphism of metabolic enzymes p450 (CYP) as a susceptibility factor for drug response, toxicity, and cancer risk. Arh Hig Rada Toksikol 2009; 60: 217-242.
124. Kazui M, Nishiya Y, Ishizuka T, Hagihara K, Farid NA, Okazaki O, et al. Identification of the human cytochrome p450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug Metab Dispos 2010; 38: 92-99.
125. Lau WC, Gurbel PA, Watkins PB, Neer CJ, Hopp AS, Carville DG, et al. Contribution of hepatic cytochrome p450 3a4 metabolic activity to the phenomenon of clopidogrel resistance. Circulation 2004; 109: 166-171.
126. Hagedorn KA, Cooke CL, Falck JR, Mitchell BF, Davidge ST. Regulation of vascular tone during pregnancy: A novel role for the pregnane X receptor. Hypertension 2007; 49: 328-333.
127. Huang W, Zhang J, Moore DD. A traditional herbal medicine enhances bilirubin clearance by activating the nuclear receptor CAR. J Clin Invest 2004; 113: 137-143.
128. Moore LB, Goodwin B, Jones SA, Wisely GB, Serabjit-Singh CJ, Willson TM, et al. St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci USA 2000; 97: 7500-7502.
129. Cheng TO. Cardiovascular effects of danshen. Int J Cardiol 2007; 121: 9-22.
130. Yu C, Ye S, Sun H, Liu Y, Gao L, Shen C, et al. PXR-mediated transcriptional activation of CYP3a4 by cryptotanshinone and tanshinone IIa. Chem Biol Interact 2009; 177: 58-64.
131. Chang TK. Activation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR) by herbal medicines. AAPS J 2009; 11: 590-601.
132. Graham MJ, Lake BG. Induction of drug metabolism: Species differences and toxicological relevance. Toxicology 2008; 254: 184-191.
133. Folts JD. Potential health benefits from the flavonoids in grape products on vascular disease. Adv Exp Med Biol 2002; 505: 95-111.
134. Medjakovic S, Jungbauer A. Red clover isoflavones biochanin A and formononetin are potent ligands of the human aryl hydrocarbon receptor. J Steroid Biochem Mol Biol 2008; 108: 171-177.
135. Shan Y, Zhao R, Geng W, Lin N, Wang X, Du X, et al. Protective effect of sulforaphane on human vascular endothelial cells against lipopolysaccharide-induced inflammatory damage. Cardiovasc Toxicol 2010; 10: 139-145.
136. Anwar-Mohamed A, El-Kadi AO. Sulforaphane induces CYP1a1 mRNA, protein, and catalytic activity levels via an AhR-dependent pathway in murine hepatoma HEPA1c1c7 and human HEPG2 cells. Cancer Lett 2009; 275: 93-101.
137. Gielen JE, Nebert DW. Aryl hydrocarbon hydroxylase induction in mammalian liver cell culture. I: Stimulation of enzyme activity in nonhepatic cells and in hepatic cells by phenobarbital, polycyclic hydrocarbons, and 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane. J Biol Chem 1971; 246: 5189-5198.
138. Zatloukalova J, Svihalkova-Sindlerova L, Kozubik A, Krcmar P, Machala M, Vondracek J. Beta-naphthoflavone and 3'-methoxy-4'-nitroflavone exert ambiguous effects on Ah receptor-dependent cell proliferation and gene expression in rat liver 'stem-like' cells. Biochem Pharmacol 2007; 73: 1622-1634.
139. Barouki R, Coumoul X, Fernandez-Salguero PM. The aryl hydrocarbon receptor, more than a xenobiotic-interacting protein. FEBS Lett 2007; 581: 3608-3615.
140. Bittinger MA, Nguyen LP, Bradfield CA. Aspartate aminotransferase generates proagonists of the aryl hydrocarbon receptor. Mol Pharmacol 2003; 64: 550-556.
141. Zhou C, King N, Chen KY, Breslow JL. Activation of PXR induces hypercholesterolemia in wild-type and accelerates atherosclerosis in ApoE deficient mice. J Lipid Res 2009; 50: 2004-2013.
142. Sberna AL, Assem M, Xiao R, Ayers S, Gautier T, Guiu B, et al. Constitutive androstane receptor activation decreases plasma apolipoprotein B-containing lipoproteins and atherosclerosis in lowdensity lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol 2011; 31: 2232-2239.