cardioКардиологияKardiologiia0022-90402412-5660Kardiomag10.18087/cardio.2021.4.n1497cardio-1497Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИRESEARCH ARTICLESОтсутствие связи между уровнем интерлейкина-25 в сыворотке крови и острым коронарным синдромом: предварительное исследованиеLack of association between serum IL-25 levels and acute coronary syndrome: a preliminary studyhttps://orcid.org/0000-0001-9187-9943НадераНадеренNaderiNadereh

Главный научный сотрудник

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msbhnadereh@gmail.comФаршидиНаргесFarshidiNarges

младший научный сотрудник

Junior Researcher  

nargesfarshidi2017@gmail.comФаршидиХоссейнFarshidiHossein

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Senior Researcher 

farshidi@hums.ac.irМонтазергхемХоссейнMontazerghaemHossein

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hossein72mg@gmail.comРахимзаденМансаRahimzadehMahsa

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rahimzadeh91@gmail.comОтделение иммунологии медицинского факультета Хормозганского университета медицинских наук, Бендер-Аббас, Иран Исследовательский центр молекулярной медицины, Институт здоровья Хормозган, Хормозганский университет медицинских наук, Бендер-Аббас, ИранИранDepartment of Immunology, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, IranIslamic Republic of IranОтделение иммунологии медицинского факультета Хормозганского университета медицинских наук, Бендер-Аббас, ИранИранDepartment of Immunology, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, IranIslamic Republic of IranЦентр сердечно-сосудистых исследований, Университет медицинских наук Хормозган, Бендер-Аббас, ИранИранCardiovascular Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, IranIslamic Republic of IranОтделение биохимии медицинского факультета Хормозганского университета медицинских наук, Бендер-Аббас, ИранИранDepartment of Biochemistry, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, IranIslamic Republic of Iran2021030520216146065Copyright © Kardiomag, 20212021KardiomagKardiomaghttps://cardio.elpub.ru/jour/about/submissions#copyrightNoticehttps://cardio.elpub.ru/jour/article/view/1497

Цель    В настоящем исследовании впервые была оценена взаимосвязь между уровнем IL-25 и риском развития острого коронарного синдрома (ОКС) у иранских пациентов. Методы    Уровень IL-25 в сыворотке крови был измерен с помощь иммуноферментного анализа у 88 пациентов с ОКС, у 40 пациентов со стабильной стенокардией и у 50 здоровых людей из контрольной группы. Результаты    Не наблюдалось значительных различий концентрации IL-25 между пациентами со стабильной стенокардией (339,8 ± 167,6 нг / л), ОКС (329,6 ± 151,3 нг / л) и группой контроля (301,6 ± 134,8 нг / л) (р = 0,5). Также не было выявлено различий между пациентами с 1, 2 или 3 - сосудистым атеросклеротическим поражением в группах со стабильной стенокардией и ОКС. Линейный регрессионный анализ показал, что IL-25 не коррелировал с факторами риска ишемической болезни сердца в исследуемой когорте. Биохимические и демографические переменные существенно не различались между различными квартилями концентрации IL-25.Заключение    Несмотря на предыдущие исследования на мышах и людях, посвященные защитной роли IL-25 при атеросклерозе, результаты нашей работы свидетельствуют о том, что IL-25 не имеет потенциального значения для развития и лечения атеросклероза у людей.

Purpose    Here, for the first time, the possible association between IL-25 and the risk of acute coronary syndrome (ACS) in Iranian patients was investigated.Material and methods    In this study, serum IL-25 concentrations were measured with an enzyme-linked immunosorbent assay in 88 ACS patients, 40 stable angina pectoris (SAP) patients, and 50 healthy control subjects.Results    No significant differences in IL-25 concentrations were observed between SAP (340±168 ng / l), ACS (330±151 ng / l), and control (302±135 ng / l) groups (p=0.5), nor was there a difference among patients with 1, 2, or 3 vessel disease in the SAP and ACS groups. Linear regression analyses revealed that IL-25 was not correlated with coronary artery disease risk factors. Biochemical and demographic variables did not differ significantly among IL-25 quartiles.Conclusion    Despite previous murine and human studies showing a protective role of IL-25 in atherosclerosis, our results revealed that IL-25 does not have potential implications for atherosclerosis development and management in humans.

Стабильная стенокардиянестабильная стенокардияострый инфаркт миокардаострый коронарный синдромИЛ-25Acute coronary syndromeacute myocardial infarctionIL-25stable angina pectorisunstable angina pectorisКонфликт интересов не заявлен.No conflict of interest is reported.ReferencesTedgui A, Mallat Z. Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways. Physiological Reviews. 2006;86(2):515–81. DOI: 10.1152/physrev.00024.2005Tedgui A, Mallat Z. Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways. Physiological Reviews. 2006;86(2):515–81. DOI: 10.1152/physrev.00024.2005Fatkhullina AR, Peshkova IO, Koltsova EK. The role of cytokines in the development of atherosclerosis. Biochemistry (Moscow). 2016;81(11):1358–70. DOI: 10.1134/S0006297916110134Tedgui A, Mallat Z. Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways. Physiological Reviews. 2006;86(2):515–81. DOI: 10.1152/physrev.00024.2005Ait-Oufella H, Taleb S, Mallat Z, Tedgui A. Recent Advances on the Role of Cytokines in Atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology. 2011;31(5):969–79. DOI: 10.1161/ATVBAHA.110.207415Fatkhullina AR, Peshkova IO, Koltsova EK. The role of cytokines in the development of atherosclerosis. Biochemistry (Moscow). 2016;81(11):1358–70. DOI: 10.1134/S0006297916110134Mantani PT, Dunér P, Bengtsson E, Alm R, Ljungcrantz I, Söderberg I et al. IL-25 Inhibits Atherosclerosis Development in Apolipoprotein E Deficient Mice. PLOS ONE. 2015;10(1):e0117255. DOI: 10.1371/journal.pone.0117255Ait-Oufella H, Taleb S, Mallat Z, Tedgui A. Recent Advances on the Role of Cytokines in Atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology. 2011;31(5):969–79. DOI: 10.1161/ATVBAHA.110.207415Iwakura Y, Ishigame H, Saijo S, Nakae S. Functional Specialization of Interleukin-17 Family Members. Immunity. 2011;34(2):149–62. DOI: 10.1016/j.immuni.2011.02.012Mantani PT, Dunér P, Bengtsson E, Alm R, Ljungcrantz I, Söderberg I et al. IL-25 Inhibits Atherosclerosis Development in Apolipoprotein E Deficient Mice. PLOS ONE. 2015;10(1):e0117255. DOI: 10.1371/journal.pone.0117255Cheng X, Yu X, Ding Y, Fu Q, Xie J, Tang T et al. The Th17/Treg imbalance in patients with acute coronary syndrome. Clinical Immunology. 2008;127(1):89–97. DOI: 10.1016/j.clim.2008.01.009Iwakura Y, Ishigame H, Saijo S, Nakae S. Functional Specialization of Interleukin-17 Family Members. Immunity. 2011;34(2):149–62. DOI: 10.1016/j.immuni.2011.02.012Xie J, Wang J, Tang T, Chen J, Gao X, Yuan J et al. The Th17/Treg functional imbalance during atherogenesis in ApoE−/− mice. Cytokine. 2010;49(2):185–93. DOI: 10.1016/j.cyto.2009.09.007Cheng X, Yu X, Ding Y, Fu Q, Xie J, Tang T et al. The Th17/Treg imbalance in patients with acute coronary syndrome. Clinical Immunology. 2008;127(1):89–97. DOI: 10.1016/j.clim.2008.01.009Zhang S, Yuan J, Yu M, Fan H, Guo Z-Q, Yang R et al. IL-17A Facilitates Platelet Function through the ERK2 Signaling Pathway in Patients with Acute Coronary Syndrome. PLoS ONE. 2012;7(7): e40641. DOI: 10.1371/journal.pone.0040641Xie J, Wang J, Tang T, Chen J, Gao X, Yuan J et al. The Th17/Treg functional imbalance during atherogenesis in ApoE−/− mice. Cytokine. 2010;49(2):185–93. DOI: 10.1016/j.cyto.2009.09.007Saenz SA, Siracusa MC, Perrigoue JG, Spencer SP, Urban Jr JF, Tocker JE et al. IL25 elicits a multipotent progenitor cell population that promotes TH2 cytokine responses. Nature. 2010;464(7293):1362–6. DOI: 10.1038/nature08901Zhang S, Yuan J, Yu M, Fan H, Guo Z-Q, Yang R et al. IL-17A Facilitates Platelet Function through the ERK2 Signaling Pathway in Patients with Acute Coronary Syndrome. PLoS ONE. 2012;7(7): e40641. DOI: 10.1371/journal.pone.0040641Neill DR, McKenzie AN. TH9: the latest addition to the expanding repertoire of IL‐25 targets. Immunology & Cell Biology. 2010;88(5):502–4. DOI: 10.1038/icb.2010.43Saenz SA, Siracusa MC, Perrigoue JG, Spencer SP, Urban Jr JF, Tocker JE et al. IL25 elicits a multipotent progenitor cell population that promotes TH2 cytokine responses. Nature. 2010;464(7293):1362–6. DOI: 10.1038/nature08901Hams E, Locksley RM, McKenzie ANJ, Fallon PG. Cutting Edge: IL-25 Elicits Innate Lymphoid Type 2 and Type II NKT Cells That Regulate Obesity in Mice. The Journal of Immunology. 2013;191(11):5349–53. DOI: 10.4049/jimmunol.1301176Neill DR, McKenzie AN. TH9: the latest addition to the expanding repertoire of IL‐25 targets. Immunology & Cell Biology. 2010;88(5):502–4. DOI: 10.1038/icb.2010.43Yao X, Sun Y, Wang W, Sun Y. Interleukin (IL)-25: Pleiotropic roles in asthma: IL-25 and asthma. Respirology. 2016;21(4):638–47. DOI: 10.1111/resp.12707Hams E, Locksley RM, McKenzie ANJ, Fallon PG. Cutting Edge: IL-25 Elicits Innate Lymphoid Type 2 and Type II NKT Cells That Regulate Obesity in Mice. The Journal of Immunology. 2013;191(11):5349–53. DOI: 10.4049/jimmunol.1301176Kleinschek MA, Owyang AM, Joyce-Shaikh B, Langrish CL, Chen Y, Gorman DM et al. IL-25 regulates Th17 function in autoimmune inflammation. The Journal of Experimental Medicine. 2007;204(1):161–70. DOI: 10.1084/jem.20061738Yao X, Sun Y, Wang W, Sun Y. Interleukin (IL)-25: Pleiotropic roles in asthma: IL-25 and asthma. Respirology. 2016;21(4):638–47. DOI: 10.1111/resp.12707Liu D, Cao T, Wang N, Liu C, Ma N, Tu R et al. IL-25 attenuates rheumatoid arthritis through suppression of Th17 immune responses in an IL-13-dependent manner. Scientific Reports. 2016;6(1):36002. DOI: 10.1038/srep36002Kleinschek MA, Owyang AM, Joyce-Shaikh B, Langrish CL, Chen Y, Gorman DM et al. IL-25 regulates Th17 function in autoimmune inflammation. The Journal of Experimental Medicine. 2007;204(1):161–70. DOI: 10.1084/jem.20061738Su J, Chen T, Ji X-Y, Liu C, Yadav PK, Wu R et al. IL-25 Downregulates Th1/Th17 Immune Response in an IL-10–Dependent Manner in Inflammatory Bowel Disease: Inflammatory Bowel Diseases. 2013;19(4):720–8. DOI: 10.1097/MIB.0b013e3182802a76Liu D, Cao T, Wang N, Liu C, Ma N, Tu R et al. IL-25 attenuates rheumatoid arthritis through suppression of Th17 immune responses in an IL-13-dependent manner. Scientific Reports. 2016;6(1):36002. DOI: 10.1038/srep36002Caruso R, Sarra M, Stolfi C, Rizzo A, Fina D, Fantini MC et al. Interleukin-25 Inhibits Interleukin-12 Production and Th1 Cell-Driven Inflammation in the Gut. Gastroenterology. 2009;136(7):2270–9. DOI: 10.1053/j.gastro.2009.02.049Su J, Chen T, Ji X-Y, Liu C, Yadav PK, Wu R et al. IL-25 Downregulates Th1/Th17 Immune Response in an IL-10–Dependent Manner in Inflammatory Bowel Disease: Inflammatory Bowel Diseases. 2013;19(4):720–8. DOI: 10.1097/MIB.0b013e3182802a76Emamaullee JA, Davis J, Merani S, Toso C, Elliott JF, Thiesen A et al. Inhibition of Th17 Cells Regulates Autoimmune Diabetes in NOD Mice. Diabetes. 2009;58(6):1302–11. DOI: 10.2337/db08-1113Caruso R, Sarra M, Stolfi C, Rizzo A, Fina D, Fantini MC et al. Interleukin-25 Inhibits Interleukin-12 Production and Th1 Cell-Driven Inflammation in the Gut. Gastroenterology. 2009;136(7):2270–9. DOI: 10.1053/j.gastro.2009.02.049Mantani PT, Dunér P, Bengtsson E, Ljungcrantz I, Sundius L, To F et al. Interleukin-25 (IL-25) has a protective role in atherosclerosis development in the aortic arch in mice. Journal of Biological Chemistry. 2018;293(18):6791–801. DOI: 10.1074/jbc.RA117.000292Emamaullee JA, Davis J, Merani S, Toso C, Elliott JF, Thiesen A et al. Inhibition of Th17 Cells Regulates Autoimmune Diabetes in NOD Mice. Diabetes. 2009;58(6):1302–11. DOI: 10.2337/db08-1113Gibbons RJ, Balady GJ, Timothy Bricker J, Chaitman BR, Fletcher GF, Froelicher VF et al. ACC/AHA 2002 guideline update for exercise testing: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). Journal of the American College of Cardiology. 2002;40(8):1531–40. DOI: 10.1016/S0735-1097(02)02164-2Mantani PT, Dunér P, Bengtsson E, Ljungcrantz I, Sundius L, To F et al. Interleukin-25 (IL-25) has a protective role in atherosclerosis development in the aortic arch in mice. Journal of Biological Chemistry. 2018;293(18):6791–801. DOI: 10.1074/jbc.RA117.000292Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease. The American Journal of Cardiology. 1983;51(3):606. DOI: 10.1016/S0002-9149(83)80105-2Gibbons RJ, Balady GJ, Timothy Bricker J, Chaitman BR, Fletcher GF, Froelicher VF et al. ACC/AHA 2002 guideline update for exercise testing: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). Journal of the American College of Cardiology. 2002;40(8):1531–40. DOI: 10.1016/S0735-1097(02)02164-2Fort MM, Cheung J, Yen D, Li J, Zurawski SM, Lo S et al. IL-25 Induces IL-4, IL-5, and IL-13 and Th2-Associated Pathologies In Vivo. Immunity. 2001;15(6):985–95. DOI: 10.1016/S1074-7613(01)00243-6Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease. The American Journal of Cardiology. 1983;51(3):606. DOI: 10.1016/S0002-9149(83)80105-2Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H et al. Innate production of TH2 cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphoid cells. Nature. 2010;463(7280):540–4. DOI:10.1038/nature08636Fort MM, Cheung J, Yen D, Li J, Zurawski SM, Lo S et al. IL-25 Induces IL-4, IL-5, and IL-13 and Th2-Associated Pathologies In Vivo. Immunity. 2001;15(6):985–95. DOI: 10.1016/S1074-7613(01)00243-6Neill DR, Wong SH, Bellosi A, Flynn RJ, Daly M, Langford TKA et al. Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature. 2010;464(7293):1367–70. DOI: 10.1038/nature08900Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H et al. Innate production of TH2 cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphoid cells. Nature. 2010;463(7280):540–4. DOI:10.1038/nature08636Price AE, Liang H-E, Sullivan BM, Reinhardt RL, Eisley CJ, Erle DJ et al. Systemically dispersed innate IL-13-expressing cells in type 2 immunity. Proceedings of the National Academy of Sciences. 2010;107(25):11489–94. DOI: 10.1073/pnas.1003988107Neill DR, Wong SH, Bellosi A, Flynn RJ, Daly M, Langford TKA et al. Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature. 2010;464(7293):1367–70. DOI: 10.1038/nature08900Huber SA, Sakkinen P, David C, Newell MK, Tracy RP. T Helper–Cell Phenotype Regulates Atherosclerosis in Mice Under Conditions of Mild Hypercholesterolemia. Circulation. 2001;103(21):2610–6. DOI: 10.1161/01.CIR.103.21.2610Price AE, Liang H-E, Sullivan BM, Reinhardt RL, Eisley CJ, Erle DJ et al. Systemically dispersed innate IL-13-expressing cells in type 2 immunity. Proceedings of the National Academy of Sciences. 2010;107(25):11489–94. DOI: 10.1073/pnas.1003988107Butcher MJ, Gjurich BN, Phillips T, Galkina EV. The IL-17A/IL17RA Axis Plays a Proatherogenic Role via the Regulation of Aortic Myeloid Cell Recruitment. Circulation Research. 2012;110(5):675–87. DOI: 10.1161/CIRCRESAHA.111.261784Huber SA, Sakkinen P, David C, Newell MK, Tracy RP. T Helper–Cell Phenotype Regulates Atherosclerosis in Mice Under Conditions of Mild Hypercholesterolemia. Circulation. 2001;103(21):2610–6. DOI: 10.1161/01.CIR.103.21.2610Erbel C, Chen L, Bea F, Wangler S, Celik S, Lasitschka F et al. Inhibition of IL-17A Attenuates Atherosclerotic Lesion Development in ApoE-Deficient Mice. The Journal of Immunology. 2009;183(12):8167–75. DOI: 10.4049/jimmunol.0901126Butcher MJ, Gjurich BN, Phillips T, Galkina EV. The IL-17A/IL17RA Axis Plays a Proatherogenic Role via the Regulation of Aortic Myeloid Cell Recruitment. Circulation Research. 2012;110(5):675–87. DOI: 10.1161/CIRCRESAHA.111.261784Smith E, Prasad K-MR, Butcher M, Dobrian A, Kolls JK, Ley K et al. Blockade of Interleukin-17A Results in Reduced Atherosclerosis in Apolipoprotein E–Deficient Mice. Circulation. 2010;121(15):1746–55. DOI: 10.1161/CIRCULATIONAHA.109.924886Erbel C, Chen L, Bea F, Wangler S, Celik S, Lasitschka F et al. Inhibition of IL-17A Attenuates Atherosclerotic Lesion Development in ApoE-Deficient Mice. The Journal of Immunology. 2009;183(12):8167–75. DOI: 10.4049/jimmunol.0901126de Boer OJ, van der Meer JJ, Teeling P, van der Loos CM, Idu MM, van Maldegem F et al. Differential expression of interleukin-17 family cytokines in intact and complicated human atherosclerotic plaques. The Journal of Pathology. 2010;220(4):499–508. DOI: 10.1002/path.2667Smith E, Prasad K-MR, Butcher M, Dobrian A, Kolls JK, Ley K et al. Blockade of Interleukin-17A Results in Reduced Atherosclerosis in Apolipoprotein E–Deficient Mice. Circulation. 2010;121(15):1746–55. DOI: 10.1161/CIRCULATIONAHA.109.924886Xu Y, Ye J, Wang M, Liu J, Wang Z, Jiang H et al. Interleukin-25 increases in human coronary artery disease and is associated with the severity of coronary stenosis. The Anatolian Journal of Cardiology. 2020;23(3):151–9. DOI: 10.14744/AnatolJCardiol.2019.24265de Boer OJ, van der Meer JJ, Teeling P, van der Loos CM, Idu MM, van Maldegem F et al. Differential expression of interleukin-17 family cytokines in intact and complicated human atherosclerotic plaques. The Journal of Pathology. 2010;220(4):499–508. DOI: 10.1002/path.2667Xu Y, Ye J, Wang M, Liu J, Wang Z, Jiang H et al. Interleukin-25 increases in human coronary artery disease and is associated with the severity of coronary stenosis. The Anatolian Journal of Cardiology. 2020;23(3):151–9. DOI: 10.14744/AnatolJCardiol.2019.24265Xu Y, Ye J, Wang M, Liu J, Wang Z, Jiang H et al. Interleukin-25 increases in human coronary artery disease and is associated with the severity of coronary stenosis. The Anatolian Journal of Cardiology. 2020;23(3):151–9. DOI: 10.14744/AnatolJCardiol.2019.24265

The authors declare that there are no conflicts of interest present.