Burcu BAYOĞLU, Ahmet DİRİCAN, Serkan Burç DEŞER, Berk ARAPİ, Müjgan CENGİZ, Caner ARSLAN, Yerik JUNUSBEKOV

Increased Expression of Interleukin-18 mRNA is Associated with Carotid Artery Stenosis

Background: Carotid artery stenosis is the atherosclerotic narrowingof the proximal internal carotid artery and one of the primary causesof stroke. Elevated expression of the pleiotropic proinflammatorycytokine interleukin-18 has been demonstrated in humanatherosclerotic plaques.Aims: To investigate whether the mRNA expression levels ofinterleukin-18 and interleukin-18-binding protein and interleukin-18−137 G/C (rs187238) variants are associated with carotid arterystenosis development.Study Design: Case-control study.Methods: The mRNA expression levels of interleukin-18 andinterleukin-18-binding protein and interleukin-18 rs187238 variantswere evaluated by quantitative real-time polymerase chain reactionand real-time polymerase chain reaction, respectively, in the peripheralblood mononuclear cells of 70 patients with carotid artery stenosis (36symptomatic, 34 asymptomatic) and 75 healthy controls.Results: Interleukin-18 mRNA expression was significantly increasedin carotid artery stenosis patients compared to that in healthy controls(p=0.01). However, no significant difference was observed betweeninterleukin-18-binding protein mRNA expression levels in patientswith carotid artery stenosis and those in controls (p=0.101). Internalcarotid artery stenosis severity was significantly higher in symptomaticpatients than that in asymptomatic patients (p

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Jefferis BJ, Papacosta O, Owen CG, Wannamethee SG, Humphries SE, Woodward M, et al. Interleukin 18 and coronary heart disease: Prospective study and systematic review. Atherosclerosis 2011;217:227-33.
Deser SB, Bayoglu B, Besirli K, Cengiz M, Arapi B, Junusbekov Y, et al. Increased IL18 mRNA levels in peripheral artery disease and its association with triglyceride and LDL cholesterol levels: a pilot study. Heart Vessels 2016;31:976- 84.
Wang J, Sun C, Gerdes N, Liu C, Liao M, Liu J, et al. Interleukin 18 function in atherosclerosis is mediated by the interleukin 18 receptor and the Na-Cl co-transporter. Nat Med 2015;21:820-6.
Chang CH, Fan PC, Lin CY, Yang CH, Chen YT, Chang SW, et al. Elevation of Interleukin-18 Correlates with Cardiovascular, Cerebrovascular, and Peripheral Vascular Events: A Cohort Study of Hemodialysis Patients. Medicine (Baltimore) 2015;94:e1836.
Yan H, Ma Y, Li Y, Zheng X, Lv P, Zhang Y, et al. Insulin inhibits inflammation and promotes atherosclerotic plaque stability via PI3K-Akt pathway activation. Immunol Lett 2016;170:7-14.
Hernesniemi JA, Heikkilä A, Raitakari OT, Kähönen M, Juonala M, Hutri-Kähönen N, et al. Interleukin-18 gene polymorphism and markers of subclinical atherosclerosis. The Cardiovascular Risk in Young Finns Study. Ann Med 2010;42:223-30.
Gerdes N, Sukhova GK, Libby P, Reynolds RS, Young JL, Schönbeck U. Expression of Interleukin (IL)-18 and functional IL-18 receptor on human vascular endothelial cells, smooth muscle cells, and macrophages: implications for atherogenesis. J Exp Med 2002;195:245-57.
Zhang N, Yu JT, Yu NN, Lu RC, Ma T, Wang ND, et al. Interleukin-18 promoter polymorphisms and risk of ischemic stroke. Brain Res Bull 2010;81:590-4.
Liu W, Tang Q, Jiang H, Ding X, Liu Y, Zhu R, et al. Promoter polymorphism of interleukin-18 in angiographically proven coronary artery disease. Angiology 2009;60:180-5.
Bayoglu B, Arslan C, Tel C, Ulutin T, Dirican A, Deser SB, et al. Genetic variants rs1994016 and rs3825807 in ADAMTS7 affect its mRNA expression in atherosclerotic occlusive peripheral arterial disease. J Clin Lab Anal 2018:32.
Yamagami H, Kitagawa K, Hoshi T, Furukado S, Hougaku H, Nagai Y, et al. Associations of serum IL-18 levels with carotid intima-media thickness. Arterioscler Thromb Vasc Biol 2005;25:1458-62.
Giedraitis V, He B, Huang WX, Hillert J. Cloning and mutation analysis of the human IL-18 promoter: a possible role of polymorphisms in expression regulation. J Neuroimmunol 2001;112:146-52.
Arimitsu J, Hirano T, Higa S, Kawai M, Naka T, Ogata A, et al. IL-18 gene polymorphisms affect IL-18 production capability by monocytes. Biochem Biophys Res Commun 2006;342:1413-6.
Liang XH, Cheung W, Heng CK, Wang DY. Reduced transcriptional activity in individuals with IL-18 gene variants detected from functional but not association study. Biochem Biophys Res Commun 2005;338:736-41.
Novick D, Kim S, Kaplanski G, Dinarello CA. Interleukin-18, more than a Th1 cytokine. Semin Immunol 2013;25:439-48.
O'Brien LC, Mezzaroma E, Van Tassell BW, Marchetti C, Carbone S, Abbate A, et al. Interleukin-18 as a therapeutic target in acute myocardial infarction and heart failure. Mol Med 2014;20:221-9.
Krishnan SM, Sobey CG, Latz E, Mansell A, Drummond GR. IL-1β and IL-18: inflammatory markers or mediators of hypertension? Br J Pharmacol 2014;171:5589- 602.
Dinarello CA, Novick D, Kim S, Kaplanski G. Interleukin-18 and IL-18 binding protein. Front Immunol 2013;4:289.
Mallat Z, Corbaz A, Scoazec A, Besnard S, Leseche G, Chvatchko Y, et al. Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability. Circulation 2001;104:1598-603.
Mallat Z, Corbaz A, Scoazec A, Graber P, Alouani S, Esposito B, et al. Interleukin-18/ interleukin-18 binding protein signaling modulates atherosclerotic lesion development and stability. Circ Res 2001;89:41-5.
Seta Y, Kanda T, Tanaka T, Arai M, Sekiguchi K, Yokoyama T, et al. Interleukin-18 in acute myocardial infarction. Heart 2000;84:668.
Conti B, Sugama S, Kim Y, Tinti C, Kim H, Baker H, et al. Modulation of IL-18 production in the adrenal cortex following acute ACTH or chronic corticosterone treatment. Neuroimmunomodulation 2000;8:1-7.
Conti B, Jahng JW, Tinti C, Son JH, Joh TH. Induction of interferon-gamma inducing factor in the adrenal cortex. J Biol Chem 1997;272:2035-7.
Reddy P. Interleukin-18: recent advances. Curr Opin Hematol 2004;11:405-10.
Dinarello CA. Interleukin 1 and interleukin 18 as mediators of inflammation and the aging process. Am J Clin Nutr 2006;83:447-55.
Okamura H, Tsutsui H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, et al. Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 1995;378:88-91.
Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med 1999;340:115-26.
Golledge J, Siew DA. Identifying the carotid ‘high risk’ plaque: is it still a riddle wrapped up in an enigma? Eur J Vasc Endovasc Surg 2008;35:2-8.
Daly C, Rodriguez HE. Carotid artery occlusive disease. Surg Clin North Am 2013;93:813-32.
Della-Morte D, Guadagni F, Palmirotta R, Testa G, Caso V, Paciaroni M, et al. Genetics of ischemic stroke, stroke-related risk factors, stroke precursors and treatments. Pharmacogenomics 2012;13:595-613.