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

Year 2018, Volume: 35 Issue: 3, 250 - 255, 01.05.2018

Berk Arapi Burcu Bayoğlu Müjgan Cengiz Ahmet Dirican Serkan Burç Deser Yerik Junusbekov Caner Arslan

Abstract

Background: Carotid artery stenosis is the atherosclerotic narrowing of the proximal internal carotid artery and one of the primary causes of stroke. Elevated expression of the pleiotropic proinflammatory cytokine interleukin-18 has been demonstrated in human atherosclerotic plaques.Aims: To investigate whether the mRNA expression levels of interleukin-18 and interleukin-18-binding protein and interleukin-18 −137 G/C (rs187238) variants are associated with carotid artery stenosis development.Study Design: Case-control study.Methods: The mRNA expression levels of interleukin-18 and interleukin-18-binding protein and interleukin-18 rs187238 variants were evaluated by quantitative real-time polymerase chain reaction and real-time polymerase chain reaction, respectively, in the peripheral blood mononuclear cells of 70 patients with carotid artery stenosis (36 symptomatic, 34 asymptomatic) and 75 healthy controls.Results: Interleukin-18 mRNA expression was significantly increased in carotid artery stenosis patients compared to that in healthy controls (p=0.01). However, no significant difference was observed between interleukin-18-binding protein mRNA expression levels in patients with carotid artery stenosis and those in controls (p=0.101). Internal carotid artery stenosis severity was significantly higher in symptomatic patients than that in asymptomatic patients (p<0.001). A significant relationship was identified between interleukin-18 expression and internal carotid artery stenosis severity in patients with carotid artery stenosis (p=0.051). Interleukin-18 rs187238 polymorphism genotype frequencies did not significantly differ between patients with carotid artery stenosis and controls (p=0.246). A significant difference was identified between interleukin-18-binding protein gene expression and symptomatic and asymptomatic patients (p=0.026), but there was no difference in interleukin-18 expression between the symptomatic and asymptomatic subgroups (p=0.397).Conclusion: Interleukin-18 mRNA expression may affect carotid artery stenosis etiopathogenesis and internal carotid artery stenosis severity and also may play a mechanistic role in the pathogenesis of carotid artery stenosis, influencing the appearance of symptoms.

Keywords

Carotid artery, gene expression, interleukin-18, interleukin-18-binding protein, stenosis

References

• 1. 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.
• 2. Daly C, Rodriguez HE. Carotid artery occlusive disease. Surg Clin North Am 2013;93:813-32.
• 3. 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.
• 4. Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med 1999;340:115-26.
• 5. 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.
• 6. Dinarello CA. Interleukin 1 and interleukin 18 as mediators of inflammation and the aging process. Am J Clin Nutr 2006;83:447-55.
• 7. Reddy P. Interleukin-18: recent advances. Curr Opin Hematol 2004;11:405-10.
• 8. 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.
• 9. 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.
• 10. Seta Y, Kanda T, Tanaka T, Arai M, Sekiguchi K, Yokoyama T, et al. Interleukin-18 in acute myocardial infarction. Heart 2000;84:668.
• 11. 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.
• 12. 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.
• 13. Dinarello CA, Novick D, Kim S, Kaplanski G. Interleukin-18 and IL-18 binding protein. Front Immunol 2013;4:289.
• 14. 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.
• 15. 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.
• 16. Novick D, Kim S, Kaplanski G, Dinarello CA. Interleukin-18, more than a Th1 cytokine. Semin Immunol 2013;25:439-48.
• 17. 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.
• 18. 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.
• 19. 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.
• 20. 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.
• 21. 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.
• 22. 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.
• 23. 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.