Aryl hydrocarbon receptor pathway: Role, regulation and intervention in atherosclerosis therapy (Review)

Zhu,Kaixi; Meng,Qingqi; Zhang,Zhi; Yi,Tao; He,Yuan; Zheng,Jing; Lei,Wei

doi:10.3892/mmr.2019.10748

Aryl hydrocarbon receptor pathway: Role, regulation and intervention in atherosclerosis therapy (Review)

Authors:
- Kaixi Zhu
- Qingqi Meng
- Zhi Zhang
- Tao Yi
- Yuan He
- Jing Zheng
- Wei Lei
View Affiliations

Affiliations: Cardiovascular Medicine Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China, Department of Orthopedics, Guangzhou Red Cross Hospital, Guangzhou, Guangdong 510000, P.R. China, Department of Vascular, Thyroid and Breast Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China, Laboratory of Cardiovascular Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China, Department of Obstetrics and Gynecology, University of Wisconsin, Madison, WI 53715, USA
Published online on: October 16, 2019 https://doi.org/10.3892/mmr.2019.10748
Pages: 4763-4773
Copyright : © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aryl hydrocarbon receptor (AhR) is a ligand‑activated transcription factor originally isolated and characterized as the dioxin or xenobiotic receptor. With the discovery of endogenous ligands and studies of AhR knockout mice, AhR has been found to serve an important role in several biological processes, including immune responses and developmental and pathological regulation. In particular, it has been considered as a new major player in cardiovascular diseases. Recent studies have revealed that the development of atherosclerosis is closely associated with AhR function. However, the roles of the AhR in the pathological development of atherosclerosis and atherosclerosis‑associated diseases remain unclear. The current review presents the molecular mechanisms involved in the regulation of AhR expression during inflammation, oxidative stress and lipid deposition. Additionally, the role of the AhR in atherosclerosis and atherosclerosis‑associated diseases is reviewed.

View Figures

View References

1	Conney AH, Miller EC and Miller JA: The metabolism of methylated aminoazo dyes v. evidence for induction of enzyme synthesis in the rat by 3-methylcholanthre. Cancer Res. 16:450–459. 1956.PubMed/NCBI
2	Hu B, Huang H, Wei Q, Ren M, Mburu DK, Tian X and Su J: Transcription factors CncC/Maf and AhR/ARNT coordinately regulate the expression of multiple GSTs conferring resistance to chlorpyrifos and cypermethrin in spodoptera exigua. Pest Manag Sci. 75:2009–2019. 2019. View Article : Google Scholar : PubMed/NCBI
3	Higgins LG and Hayes JD: Mechanisms of induction of cytosolic and microsomal glutathione transferase (GST) genes by xenobiotics and pro-inflammatory agents. Drug Metab Rev. 43:92–137. 2011. View Article : Google Scholar : PubMed/NCBI
4	De Anna JS, Leggieri LR, Arias Darraz L, Cárcamo JG, Venturino A and Luquet CM: Effects of sequential exposure to water accommodated fraction of crude oil and chlorpyrifos on molecular and biochemical biomarkers in rainbow trout. Comp Biochem Physiol C Toxicol Pharmacol. 212:47–55. 2018. View Article : Google Scholar : PubMed/NCBI
5	Davisson MT: Rules and guidelines for genetic nomenclature in mice: Excerpted version. Transgenic Res. 6:309–319. 1997. View Article : Google Scholar : PubMed/NCBI
6	Baricza E, Tamási V, Marton N, Buzás EI and Nagy G: The emerging role of aryl hydrocarbon receptor in the activation and differentiation of Th17 cells. Cell Mol Life Sci. 73:95–117. 2016. View Article : Google Scholar : PubMed/NCBI
7	Schmidt JV and Bradfield CA: Ah receptor signaling pathways. Annu Rev Cell Dev Biol. 12:55–89. 1996. View Article : Google Scholar : PubMed/NCBI
8	Go RE, Hwang KA and Choi KC: Cytochrome P450 1 family and cancers. J Steroid Biochem Mol Biol. 147:24–30. 2015. View Article : Google Scholar : PubMed/NCBI
9	Zhang N: The role of endogenous aryl hydrocarbon receptor signaling in cardiovascular physiology. J Cardiovasc Dis Res. 2:91–95. 2011. View Article : Google Scholar : PubMed/NCBI
10	Curran CP, Altenhofen E, Ashworth A, Brown A, Kamau-Cheggeh C, Curran M, Evans A, Floyd R, Fowler J, Garber H, et al: Ahr^dCyp1a2(−/−) mice show increased susceptibility to PCB-induced developmental neurotoxicity. Neurotoxicology. 33:1436–1442. 2012. View Article : Google Scholar : PubMed/NCBI
11	Bock KW: From TCDD-mediated toxicity to searches of physiologic AHR functions. Biochem Pharmacol. 155:419–424. 2018. View Article : Google Scholar : PubMed/NCBI
12	Tian Y, Rabson AB and Gallo MA: Ah receptor and NF-κB interactions: Mechanisms and physiological implications. Chem Biol Interact. 141:97–115. 2002. View Article : Google Scholar : PubMed/NCBI
13	Stejskalova L, Dvorak Z and Pavek P: Endogenous and exogenous ligands of aryl hydrocarbon receptor: Current state of art. Curr Drug Metab. 12:198–212. 2011. View Article : Google Scholar : PubMed/NCBI
14	Lamas B, Natividad JM and Sokol H: Aryl hydrocarbon receptor and intestinal immunity. Mucosal Immunol. 11:1024–1038. 2018. View Article : Google Scholar : PubMed/NCBI
15	Wakamatsu T, Yamamoto S, Ito T, Sato Y, Matsuo K, Takahashi Y, Kaneko Y, Goto S, Kazama JJ, Gejyo F and Narita I: Indoxyl sulfate promotes macrophage IL-1β production by activating aryl hydrocarbon receptor/NF-κ/MAPK cascades, but the NLRP3 inflammasome was not activated. Toxins (Basel). 10:E1242018. View Article : Google Scholar : PubMed/NCBI
16	Nishiumi S, Yamamoto N, Kodoi R, Fukuda I, Yoshida K and Ashida H: Antagonistic and agonistic effects of indigoids on the transformation of an aryl hydrocarbon receptor. Arch Biochem Biophys. 470:187–199. 2008. View Article : Google Scholar : PubMed/NCBI
17	Peter Guengerich F, Martin MV, McCormick WA, Nguyen LP, Glover E and Bradfield CA: Aryl hydrocarbon receptor response to indigoids in vitro and in vivo. Arch Biochem Biophys. 423:309–316. 2004. View Article : Google Scholar : PubMed/NCBI
18	Li W, Li Y, Sun R, Zhou S, Li M, Feng M and Xie Y: Dual character of flavonoids in attenuating and aggravating ischemia-reperfusion-induced myocardial injury. Exp Ther Med. 14:1307–1314. 2017. View Article : Google Scholar : PubMed/NCBI
19	Hubbard TD, Murray IA and Perdew GH: Indole and tryptophan metabolism: Endogenous and dietary routes to Ah Receptor activation. Drug Metab Dispos. 43:1522–1535. 2015. View Article : Google Scholar : PubMed/NCBI
20	Kewley RJ, Whitelaw ML and Chapman-Smith A: The mammalian basic helix-loop-helix/PAS family of transcriptional regulators. Int J Biochem Cell Biol. 36:189–204. 2004. View Article : Google Scholar : PubMed/NCBI
21	Bock KW: Human AHR functions in vascular tissue: Pro- and anti-inflammatory responses of AHR agonists in atherosclerosis. Biochem Pharmacol. 159:116–120. 2019. View Article : Google Scholar : PubMed/NCBI
22	Schmidt JV, Su GH, Reddy JK, Simon MC and Bradfield CA: Characterization of a murine ahR null allele: Involvement of the Ah receptor in hepatic growth and development. Proc Natl Acad Sci USA. 93:6731–6736. 1996. View Article : Google Scholar : PubMed/NCBI
23	Xu CX, Wang C, Zhang ZM, Jaeger CD, Krager SL, Bottum KM, Liu J, Liao DF and Tischkau SA: Aryl hydrocarbon receptor deficiency protects mice from diet-induced adiposity and metabolic disorders through increased energy expenditure. Int J Obes (Lond). 39:1300–1309. 2015. View Article : Google Scholar : PubMed/NCBI
24	Gutiérrez-Vázquez C and Quintana FJ: Regulation of the immune response by the aryl hydrocarbon receptor. Immunity. 48:19–33. 2018. View Article : Google Scholar : PubMed/NCBI
25	Brinchmann BC, Skuland T Rambøl MH, Szoke K, Brinchmann JE, Gutleb AC, Moschini E, Kubátová A, Kukowski K, Le Ferrec E, et al: Lipophilic components of diesel exhaust particles induce Pro-inflammatory responses in human endothelial cells through AhR dependent pathway(s). Part Fibre Toxicol. 15:212018. View Article : Google Scholar : PubMed/NCBI
26	Yu Y, Liu Q, Guo S, Zhang Q, Tang J, Liu G, Kong D, Li J, Yan S, Wang R, et al: 2,3,7,8-Tetrachlorodibenzo-p-dioxin promotes endothelial cell apoptosis through activation of EP3/p38MAPK/Bcl-2 pathway. J Cell Mol Med. 21:3540–3551. 2017. View Article : Google Scholar : PubMed/NCBI
27	Yan ZQ and Hansson GK: Innate immunity, macrophage activation, and atherosclerosis. Immunol Rev. 219:187–203. 2007. View Article : Google Scholar : PubMed/NCBI
28	Ross R: Atherosclerosis-an inflammatory disease. N Engl J Med. 340:115–126. 1999. View Article : Google Scholar : PubMed/NCBI
29	Vogel CF, Khan EM, Leung PS, Gershwin ME, Chang WL, Wu D, Haarmann-Stemmann T, Hoffmann A and Denison MS: Cross-talk between aryl hydrocarbon receptor and the inflammatory response: A role for nuclear factor-κB. J Biol Chem. 289:1866–1875. 2014. View Article : Google Scholar : PubMed/NCBI
30	Vogel CF, Sciullo E, Wong P, Kuzmicky P, Kado N and Matsumura F: Induction of proinflammatory cytokines and C-reactive protein in human macrophage cell line U937 exposed to air pollution particulates. Environ Health Perspect. 113:1536–1541. 2005. View Article : Google Scholar : PubMed/NCBI
31	Ledda A, González M, Gulfo J, Díaz Ludovico I, Ramella N, Toledo J, Garda H, Grasa M and Esteve M: Decreased OxLDL uptake and cholesterol efflux in THP1 cells elicited by cortisol and by cortisone through 11β-hydroxysteroid dehydrogenase type 1. Atherosclerosis. 250:84–94. 2016. View Article : Google Scholar : PubMed/NCBI
32	Huang Y, Du KL, Guo PY, Zhao RM, Wang B, Zhao XL and Zhang CQ: IL-16 regulates macrophage polarization as a target gene of mir-145-3p. Mol Immunol. 107:1–9. 2019. View Article : Google Scholar : PubMed/NCBI
33	Sieve I, Ricke-Hoch M, Kasten M, Battmer K, Stapel B, Falk CS, Leisegang MS, Haverich A Scherr M and Hilfiker-Kleiner D: A positive feedback loop between IL-1β, LPS and NEU1 may promote atherosclerosis by enhancing a pro-inflammatory state in monocytes and macrophages. Vascul Pharmacol. 103:16–28. 2018. View Article : Google Scholar : PubMed/NCBI
34	Abdolmaleki F, Gheibi Hayat SM, Bianconi V, Johnston TP and Sahebkar A: Atherosclerosis and immunity: A perspective. Trends Cardiovasc Med. 28:S1050–1738. 2018.(Epub ahead of print).
35	Ohtsuka M, Miyashita Y and Shirai K: Lipids deposited in human atheromatous lesions induce apoptosisof human vascular smooth muscle cells. J Atheroscler Thromb. 13:256–262. 2006. View Article : Google Scholar : PubMed/NCBI
36	Baumer Y, McCurdy S, Weatherby TM, Mehta NN, Halbherr S, Halbherr P, Yamazaki N and Boisvert WA: Hyperlipidemia-induced cholesterol crystal production by endothelial cells promotes atherogenesis. Nat Commun. 8:11292017. View Article : Google Scholar : PubMed/NCBI
37	Barnes MJ and Farndale RW: Collagens and atherosclerosis. Exp Gerontol. 34:513–525. 1999. View Article : Google Scholar : PubMed/NCBI
38	Chitra P, Saiprasad G, Manikandan R and Sudhandiran G: Berberine inhibits smad and non-smad signaling cascades and enhances autophagy against pulmonary fibrosis. J Mol Med (Berl). 93:1015–1031. 2015. View Article : Google Scholar : PubMed/NCBI
39	Ke S, Rabson AB, Germino JF, Gallo MA and Tian Y: Mechanism of suppression of cytochrome P-4501A1 expression by tumor necrosis Factor-α and lipopolysaccharide. J Biol Chem. 276:39638–39644. 2001. View Article : Google Scholar : PubMed/NCBI
40	Aung HH, Lame MW, Gohil K, He G, Denison MS, Rutledge JC and Wilson DW: Comparative gene responses to collected ambient particles in vitro: Endothelial responses. Physiol Genomics. 43:917–929. 2011. View Article : Google Scholar : PubMed/NCBI
41	Vogel CF and Matsumura F: A new cross-talk between the aryl hydrocarbon receptor and RelB, a member of the NF-ĸB family. Biochem Pharmacol. 77:734–745. 2009. View Article : Google Scholar : PubMed/NCBI
42	Vogel CF, Sciullo E, Li W, Wong P, Lazennec G and Matsumura F: RelB, a new partner of aryl hydrocarbon receptor-mediated transcription. Mol Endocrinol. 21:2941–2955. 2007. View Article : Google Scholar : PubMed/NCBI
43	Wang C, Petriello MC, Zhu B and Hennig B: PCB 126 induces monocyte/macrophage polarization and inflammation through ahR and NF-κB pathways. Toxicol Appl Pharmacol. 367:71–81. 2019. View Article : Google Scholar : PubMed/NCBI
44	Hennig B, Meerarani P, Slim R, Toborek M, Daugherty A, Silverstone AE and Robertson LW: Proinflammatory properties of coplanar PCBs: In vitro and in vivo evidence. Toxicol Appl Pharmacol. 181:174–183. 2002. View Article : Google Scholar : PubMed/NCBI
45	Yisireyili M, Saito S, Abudureyimu S, Adelibieke Y, Ng HY, Nishijima F, Takeshita K, Murohara T and Niwa T: Indoxyl sulfate-induced activation of (Pro)renin receptor promotes cell proliferation and tissue factor expression in vascular smooth muscle cells. PLoS One. 9:e1092682014. View Article : Google Scholar : PubMed/NCBI
46	Hennig B, Hammock BD, Slim R, Toborek M, Saraswathi V and Robertson LW: PCB-induced oxidative stress in endothelial cells: Modulation by nutritients. Int J Hyg Environ Health. 205:95–102. 2002. View Article : Google Scholar : PubMed/NCBI
47	Watanabe I, Tatebe J, Namba S, Koizumi M, Yamazaki J and Morita T: Activation of aryl hydrocarbon receptor mediates indoxyl sulfate-induced monocyte chemoattractant Protein-1 expression in human umbilical vein endothelial Cells. Circ J. 77:224–230. 2013. View Article : Google Scholar : PubMed/NCBI
48	Puga A, Barnes SJ, Chang C, Zhu H, Nephew KP, Khan SA and Shertzer HG: Activation of transcription factors activator protein-1 and nuclear factor-κB by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Biochem Pharmacol. 59:997–1005. 2000. View Article : Google Scholar : PubMed/NCBI
49	Chistiakov DA, Melnichenko AA, Myasoedova VA, Grechko AV and Orekhov AN: Mechanisms of foam cell formation in atherosclerosis. J Mol Med. 95:1153–1165. 2017. View Article : Google Scholar : PubMed/NCBI
50	Chan DC, Watts F, Ooi EM, Ji J, Johnson AG and Barrett PH: Atorvastatin and fenofibrate have comparable effects on VLDL-Apolipoprotein C-III kinetics in men with the metabolic syndrome. Arterioscler Thromb Vasc Biol. 28:1831–1837. 2008. View Article : Google Scholar : PubMed/NCBI
51	Mesnage R, Biserni M, Balu S, Frainay C, Poupin N, Jourdan F, Wozniak E, Xenakis T, Mein CA and Antoniou MN: Integrated transcriptomics and metabolomics reveal signatures of lipid metabolism dysregulation in hepaRG liver cells exposed to PCB 126. Arch Toxicol. 92:2533–2547. 2018. View Article : Google Scholar : PubMed/NCBI
52	Podechard N, Le Ferrec E, Rebillard A, Fardel O and Lecureur V: NPC1 repression contributes to lipid accumulation in human macrophages exposed to environmental aryl hydrocarbons. Cardiovasc Res. 82:361–370. 2009. View Article : Google Scholar : PubMed/NCBI
53	Ambolet-Camoit A, Ottolenghi C, Leblanc A, Kim MJ, Letourneur F, Jacques S, Cagnard N, Guguen-Guillouzo C, Barouki R and Aggerbeck M: Two persistent organic pollutants which act through different xenosensors (alpha-endosulfan and 2,3,7,8 tetrachlorodibenzo-p-dioxin) interact in a mixture and downregulate multiple genes involved in human hepatocyte lipid and glucose. Biochimie. 116:79–91. 2015. View Article : Google Scholar : PubMed/NCBI
54	Yao L, Wang C, Zhang X, Peng L, Liu W, Zhang X, Liu Y, He J, Jiang C, Ai D and Zhu Y: Hyperhomocysteinemia activates the aryl hydrocarbon receptor/CD36 pathway to promote hepatic steatosis in mice. Hepatology. 64:92–105. 2016. View Article : Google Scholar : PubMed/NCBI
55	Van Breda SGJ, Claessen SMH, van Herwijnen M, Theunissen DHJ, Jennen DGJ, de Kok TMCM and Kleinjans JCS: Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 393:160–170. 2018. View Article : Google Scholar : PubMed/NCBI
56	Zhang L, Hatzakis E, Nichols RG, Hao R, Correll J, Smith PB, Chiaro CR, Perdew GH and Patterson AD: Metabolomics reveals that aryl hydrocarbon receptor activation by environmental chemicals induces systemic metabolic dysfunction in mice. Environ Sci Technol. 49:8067–8077. 2015. View Article : Google Scholar : PubMed/NCBI
57	Lu P, Yan J, Liu K, Garbacz WG, Wang P, Xu M, Ma X and Xie W: Activation of aryl hydrocarbon receptor dissociates fatty liver from insulin resistance by inducing FGF21. Hepatology. 61:1908–1919. 2015. View Article : Google Scholar : PubMed/NCBI
58	Kurtz CL, Fannin EE, Toth CL, Pearson DS, Vickers KC and Sethupathy P: Inhibition of miR-29 has a significant lipid-lowering benefit through suppression of lipogenic programs in liver. Sci Rep. 5:129112015. View Article : Google Scholar : PubMed/NCBI
59	Wahlang B, Falkner KC, Gregory B, Ansert D, Young D, Conklin DJ, Bhatnagar A, McClain CJ and Cave M: Polychlorinated biphenyl 153 is a diet-dependent obesogen that worsens nonalcoholic fatty liver disease in male C57BL6/J mice. J Nutr Biochem. 24:1587–1595. 2013. View Article : Google Scholar : PubMed/NCBI
60	Han SG, Han SS, Toborek M and Hennig B: EGCG protects endothelial cells against PCB 126-induced inflammation through inhibition of AhR and induction of Nrf2-regulated genes. Toxicol Appl Pharmacol. 261:181–188. 2012. View Article : Google Scholar : PubMed/NCBI
61	Wang Z, Yang H, Ramesh A, Roberts LJ, Zhou L, Lin X, Zhao Y and Guo Z: Overexpression of Cu/Zn-superoxide dismutase and/or catalase accelerates benzo(a)pyrene detoxification by upregulation of the aryl hydrocarbon receptor in mouse endothelial cells. Free Radic Biol Med. 47:1221–1229. 2009. View Article : Google Scholar : PubMed/NCBI
62	Kim JB, Pjanic M, Nguyen T, Miller CL, Iyer D, Liu B, Wang T, Sazonova O, Carcamo-Orive I, Matic LP, et al: TCF21 and the environmental sensor aryl-hydrocarbon receptor cooperate to activate a pro-inflammatory gene expression program in coronary artery smooth muscle cells. PLoS Genet. 13:e10067502017. View Article : Google Scholar : PubMed/NCBI
63	Li X, Liu N, Wang Y, Liu J, Shi H, Qu Z, Du T, Guo B and Gu B: Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 cooperates with glycogen synthase kinase-3β to regulate osteogenesis of bone-marrow mesenchymal stem cells in type 2 diabetes. Mol Cell Endocrinol. 440:93–105. 2016. View Article : Google Scholar : PubMed/NCBI
64	Wnuk A and Kajta M: Steroid and xenobiotic receptor signalling in apoptosis and autophagy of the nervous system. Int J Mol Sci. 18:E23942017. View Article : Google Scholar : PubMed/NCBI
65	Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, Chiuve SE, Cushman M, Delling FN, Deo R, et al: American heart association council on epidemiology and prevention statistics committee and stroke statistics subcommittee: Heart disease and stroke statistics-2018 update: A report from the american heart association. Circulation. 137:e67–e492. 2018. View Article : Google Scholar : PubMed/NCBI
66	Zou JG, Ma YT, Xie X, Yang YN, Pan S, Adi D, Liu F and Chen BD: The association between CYP1A1 genetic polymorphisms and coronary artery disease in the uygur and han of China. Lipids Health Dis. 13:1452014. View Article : Google Scholar : PubMed/NCBI
67	Taspinar M, Aydos S, Sakiragaoglu O, Duzen IV, Yalcinkaya A, Oztuna D, Bardakci H, Tutar E and Sunguroglu A: Impact of genetic variations of the CYP1A1, GSTT1, and GSTM1 genes on the risk of coronary artery disease. DNA Cell Biol. 31:211–218. 2012. View Article : Google Scholar : PubMed/NCBI
68	Manfredi S, Federici C, Picano E, Botto N, Rizza A and Andreassi MG: GSTM1, GSTT1 and CYP1A1 detoxification gene polymorphisms and susceptibility to smoking-related coronary artery disease: A case-only study. Mutat Res. 621:106–112. 2007. View Article : Google Scholar : PubMed/NCBI
69	Huang S, Shui X, He Y, Xue Y, Li J, Li G, Lei W and Chen C: AhR expression and polymorphisms are associated with risk of coronary arterial disease in Chinese population. Sci Rep. 5:80222015. View Article : Google Scholar : PubMed/NCBI
70	Peng DD, Xie W and Yu ZX: Impact of interaction between CYP1A1 genetic polymorphisms and smoking on coronary artery disease in the han of China. Clin Exp Hypertens. 39:339–343. 2017. View Article : Google Scholar : PubMed/NCBI
71	Zhang X, Lv S, Guo C, Shi C, Chi Y, Zhao L, Wang G and Wang Z: Gene-gene interaction between PPARG and CYP1A1 gene on coronary artery disease in the Chinese han population. Oncotarget. 8:34398–34404. 2017.PubMed/NCBI
72	Zhang ZX and Zhang Y: Glutathione S-transferase M1 (GSTM1) null genotype and coronary artery disease risk: A meta-analysis. Int J Clin Exp Med. 7:3378–3384. 2014.PubMed/NCBI
73	Pašalić D and Marinković N: Genetic polymorphisms of the CYP1A1, GSTM1, and GSTT1 enzymes and their influence on cardiovascular risk and lipid profile in people who live near a natural gas plant. Arh Hig Rada Toksikol. 68:46–52. 2017. View Article : Google Scholar : PubMed/NCBI
74	Mir R, Bhat MA, Javaid J, Shah N, Kumar P, Sharma E, Jhu C, Basak S, Amle D, Ray PC, et al: Glutathione S-transferase M1 and T1 (rs4025935 and rs71748309) null genotypes are associated with increased susceptibility to coronary artery disease in Indian Populations. Acta Cardiol. 71:678–684. 2016. View Article : Google Scholar : PubMed/NCBI
75	Bhat MA and Gandhi G: Association of GSTT1 and GSTM1 gene polymorphisms with coronary artery disease in north Indian punjabi population: A case-control study. Postgrad Med J. 92:701–706. 2016. View Article : Google Scholar : PubMed/NCBI
76	Ramprasath T, Senthil Murugan P, Prabakaran AD, Gomathi P, Rathinavel A and Selvam GS: Potential risk modifications of GSTT1, GSTM1 and GSTP1 (glutathione-S-transferases) variants and their association to CAD in patients with type-2 diabetes. Biochem Biophys Res Commun. 407:49–53. 2011. View Article : Google Scholar : PubMed/NCBI
77	Kim SJ, Kim MG, Kim KS, Song JS, Yim SV and Chung JH: Impact of glutathione s-transferase M1 and T1 gene polymorphisms on the smoking-related coronary artery disease. J Korean Med Sci. 23:365–372. 2008. View Article : Google Scholar : PubMed/NCBI
78	Manfredi S, Calvi D, del Fiandra M, Botto N, Biagini A and Andreassi MG: Glutathione S-transferase T1- and M1-null genotypes and coronary artery disease risk in patients with type 2 diabetes mellitus. Pharmacogenomics. 10:29–34. 2009. View Article : Google Scholar : PubMed/NCBI
79	Wang LS, Tang JJ, Tang NP, Wang MW, Yan JJ, Wang QM, Yang ZJ and Wang B: Association of GSTM1 and GSTT1 gene polymorphisms with coronary artery disease in relation to tobacco smoking. Clin Chem Lab Med. 46:1720–1725. 2008. View Article : Google Scholar : PubMed/NCBI
80	Masetti S, Botto N, Manfredi S, Colombo MG, Rizza A, Vassalle C, Clerico A, Biagini A and Andreassi MG: Interactive effect of the glutathione S-transferase genes and cigarette smoking on occurrence and severity of coronary artery risk. J Mol Med (Berl). 81:488–494. 2003. View Article : Google Scholar : PubMed/NCBI
81	Kalpana C, Rajasekharan KN and Menon VP: Modulatory effects of curcumin and curcumin analog on circulatory lipid profiles during nicotine-induced toxicity in wistar rats. J Med Food. 8:246–250. 2005. View Article : Google Scholar : PubMed/NCBI
82	Li ZZ, Guo ZZ, Zhang Z, Cao QA, Zhu YJ, Yao HL, Wu LL and Dai QY: Nicotine-induced upregulation of VCAM-1, MMP-2, and MMP-9 through the α7-nAChR-JNK pathway in RAW264.7 and MOVAS cells. Mol Cell Biochem. 399:49–58. 2015. View Article : Google Scholar : PubMed/NCBI
83	Abdel Fattah S, Rizk AAE, Motawie AG, Abd El-Galil TI and El Sebaie M: Effects of nicotine on rat adrenal gland: Crosstalk between oxidative and inflammatory markers, and amelioration by melatonin. Biotech Histochem. 19:1–10. 2018.
84	O'Donnel MJ, Chin SL, Rangarajan S, Xavier D, Liu L, Zhang H, Rao-Melacini P, Zhang X, Pais P, Agapary S, et al: Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): A case control study. Lancet. 388:761–775. 2016. View Article : Google Scholar : PubMed/NCBI
85	Zhu H, Li Z, Lv J and Zhao R: Effects of cerebral small vessel disease on the outcome of patients with ischemic stroke caused by large artery atherosclerosis. Neurol Res. 40:381–390. 2018. View Article : Google Scholar : PubMed/NCBI
86	Moon KS, Lee HJ, Hong SH, Kim HM and Um JY: CYP1A1 and GSTM1/T1 genetic variation in predicting risk for cerebral infarction. J Mol Neurosci. 32:155–159. 2007. View Article : Google Scholar : PubMed/NCBI
87	Demirdöğen BC, Adali AÇ, Bek S, Demirkaya Ş and Adali O: Cytochrome P4501A1 genotypes and smoking- and hypertension-related ischemic stroke risk. Hum Exp Toxicol. 32:483–491. 2013. View Article : Google Scholar : PubMed/NCBI
88	Sultana S, Kolla VK, Peddireddy V, Jeedigunta Y, Penagaluru PK, Joshi S, Penagaluru UR and Penagaluru PR: Association of cyp1a1 gene polymorphism with ischemic stroke in south Indian population. Transl Stroke Res. 2:26–32. 2011. View Article : Google Scholar : PubMed/NCBI
89	Zhang M, Wu JM, Zhang QS, Yan DW, Ren LJ and Li WP: The association of CYP1A1 genetic polymorphisms and additional gene-gene interaction with ischemic stroke in the eastern han of China. Neurol Sci. 37:1679–1684. 2016. View Article : Google Scholar : PubMed/NCBI
90	Sindhu S, Akhter N, Kochumon S, Thomas R, Wilson A, Shenouda S, Tuomilehto J and Ahmad R: Increased expression of the innate immune receptor TLR10 in obesity and Type-2 diabetes: Association with ROS-mediated oxidative stress. Cell Physiol Biochem. 45:575–590. 2018. View Article : Google Scholar
91	Raza ST, Abbas S, Ahmad A, Ahmed F, Zaidi Zh and Mahdi F: Association of glutathione-s-transferase (GSTM1 and GSTT1) and FTO gene polymorphisms with type 2 diabetes mellitus cases in northern India. Balkan J Med Genet. 17:47–54. 2014. View Article : Google Scholar : PubMed/NCBI
92	Etemad A, Vasudevan R, Aziz AF, Yusof AK, Khazaei S, Fawzi N, Jamalpour S, Arkani M, Mohammad NA and Ismail P: Analysis of selected glutathione S-transferase gene polymorphisms in malaysian type 2 diabetes mellitus patients with and without cardiovascular disease. Genet Mol Res. 15:2016. View Article : Google Scholar :
93	Porojan MD, Bala C, Ilies R, Catana A, Popp RA and Dumitrascu DL: Combined glutathione S transferase M1/T1 null genotypes is associated with type 2 diabetes mellitus. Clujul Med. 88:159–163. 2015.PubMed/NCBI
94	Hori M, Oniki K, Ueda K, Goto S, Mihara S, Marubayashi T and Nakagawa K: Combined glutathione S-transferase T1 and M1 positive genotypes afford protection against type 2 diabetes in japanese. Pharmacogenomics. 8:1307–1314. 2007. View Article : Google Scholar : PubMed/NCBI