2658-6533Research Results in Biomedicine2658-653310.18413/2313-8955-2018-4-4-0-11537GeneticsAssociation of the ITGB3 gene T1565C polymorphism with the development of atherosclerosis and in-stent restenosis in patients with stable coronary artery diseaseAssociation of the ITGB3 gene T1565C polymorphism with the development of atherosclerosis and in-stent restenosis in patients with stable coronary artery diseaseBogatyrevaKalima B.BogatyrevaKalima B.Kalima.bogatyreva@mail.ruAzovaMadina M.AzovaMadina M.AghajanyanAnna V.AghajanyanAnna V.TskhovrebovaLeila V.TskhovrebovaLeila V.AitAissa A.AitAissa A.ShugushevZaurbek Kh.ShugushevZaurbek Kh.20184400

Background: Today, percutaneous coronary intervention (PCI) is the most effective treatment of coronary artery disease (CAD). Despite all technical advances in stent designs and techniques, in-stent restenosis (ISR) remains one of the main limiting factors of this procedure. Studies in the field of molecular cardiology have shown a significant contribution of endothelial dysfunction in the development of ISR. According to the literature, integrin beta 3 is involved in intercellular interactions, interaction with extracellular matrix; it influences the activity of smooth muscle cells, which can lead to neointimal hyperplasia. The aim of the study: To study the possibility of association of T1565C polymorphism of the ITGB3 gene with the development of restenosis after stenting of the coronary arteries. Materials and methods: Patients with CAD after PCI with drug-coated stents (n = 110) and patients with intact vessels according to angiography (n = 62) were included in the study. The repeated stenosis of the artery at the stent implantation site of more than 50% was defined as angiographic restenosis. The criteria for inclusion in the study were: age > 45 years, ethnic Russians, atherosclerosis according to the angiography of one or more arteries, patient informed consent. The genotyping for the ITGB3 T1565C polymorphism was performed using the real-time PCR. Results: The C allele and heterozygous genotype frequencies are significantly higher in groups of patients with earlier development of restenosis and diffuse CAD with occlusion. Conclusion: The minor C allele of the ITGB3 T1565C polymorphism may be considered as a predictor of diffuse CAD with the development of occlusions and ISR of the coronary arteries within the first year after stent implantation.

Background: Today, percutaneous coronary intervention (PCI) is the most effective treatment of coronary artery disease (CAD). Despite all technical advances in stent designs and techniques, in-stent restenosis (ISR) remains one of the main limiting factors of this procedure. Studies in the field of molecular cardiology have shown a significant contribution of endothelial dysfunction in the development of ISR. According to the literature, integrin beta 3 is involved in intercellular interactions, interaction with extracellular matrix; it influences the activity of smooth muscle cells, which can lead to neointimal hyperplasia. The aim of the study: To study the possibility of association of T1565C polymorphism of the ITGB3 gene with the development of restenosis after stenting of the coronary arteries. Materials and methods: Patients with CAD after PCI with drug-coated stents (n = 110) and patients with intact vessels according to angiography (n = 62) were included in the study. The repeated stenosis of the artery at the stent implantation site of more than 50% was defined as angiographic restenosis. The criteria for inclusion in the study were: age > 45 years, ethnic Russians, atherosclerosis according to the angiography of one or more arteries, patient informed consent. The genotyping for the ITGB3 T1565C polymorphism was performed using the real-time PCR. Results: The C allele and heterozygous genotype frequencies are significantly higher in groups of patients with earlier development of restenosis and diffuse CAD with occlusion. Conclusion: The minor C allele of the ITGB3 T1565C polymorphism may be considered as a predictor of diffuse CAD with the development of occlusions and ISR of the coronary arteries within the first year after stent implantation.

atherosclerosisrestenosisgene polymorphismsintegrin beta 3atherosclerosisrestenosisgene polymorphismsintegrin beta 3Список литературыNichols M, Townsend, Luengo-Fernandez R, et al. European cardiovascular disease statistics. 2012;2012. DOI: 978-2-9537898-1-2.Global Burden ofDisease Study 2013 (GBD 2013). Age-Sex Specific All-Cause and Cause-Specific Mortality 1990-2013. Seattle, United States: Institute for Health Metrics and Evaluation (IHME), 2014.Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011 Dec;58(24):e44-122. DOI: 10.1016/j.jacc.2011.08.007Marco J. Drug Eluting Stents: promises and the precautionary attitude (Grüentzig lecture at the ESC Stockholm, 2005). EuroIntervention. 2006 May;2(1):15-17.Roger VL, Go AS, Lloyd-Jones DM, et al. Statistics – 2011 Update A Report From the American Heart Association. Circulation. 2011;123(4):e18-e209.DOI:10.1161/CIR.0b013e3182009701Jukema JW, Verschuren JJ, Ahmed TA, et al. Restenosis after PCI. Part 1: pathophysiology and risk factors. Nat Rev Cardiol. 2012;9:53-62.Indolfi C, Pavia M, Angelillo IF. Drug-eluting stents versus bare metal stents in percutaneous coronary interventions (a meta-analysis). Am J Cardiol. 2005 May;95(10):1146-1152. DOI: https://doi.org/10.1016/j.amjcard.2005.01.040Gunn J, Arnold N, Chan KH, et al. Coronary artery stretch versus deep injury in the development of in-stent neointima. Heart. 2002;88:401-405. DOI: http://dx.doi.org/10.1136/heart.88.4.401Virmani R, Farb A, Weber DK, et al. Morphological predictors of restenosis after coronary stenting in humans. Circulation. 2002;105:2974-2980. DOI: 10.1161/01.CIR.0000019071.72887.BDDe Vita A, Milo M, Sestito A, et al. Association of coronary microvascular dysfunction with restenosis of left anterior descending coronary artery disease treated by percutaneous intervention. Int J Cardiol. 2016;219:322-325. DOI: https://doi.org/10.1016/j.ijcard.2016.06.031Boyle CJ, Lennon AB, Prendergast PJ. In silico prediction of the mechanobiological response of arterial tissue: application to angioplasty and Stenting. J. Biomech. Eng. 2011;133(8):81001. DOI:10.1115/1.4004492.Boyle CJ, Lennon AB, Early M, et al. Computational simulation methodologies for mechanobiological modelling: a cell-centred approach to neointima development in stents. Philos Trans A Math Phys Eng Sci. 2010;368(1921):2919-2935. DOI: 10.1098/rsta.2010.0071Munk PS, Butt N, Larsen A. Endothelial dysfunction predicts clinical restenosis after percutaneous coronary intervention. Scand Cardiovasc J. 2011;45(3):139-45. DOI: https://doi.org/10.3109/14017431.2011.564646Knowles JW, Wang H, Itakura H, et al. Association of polymorphisms in platelet and hemostasis system genes with acute myocardial infarction. Am Heart J. 2007;154(6):1052-8. DOI: https://doi.org/10.1016/j.ahj.2007.05.021Di Paola J, Jugessur A, Goldman T, et al. Platelet glycoprotein Ibα and integrin α2β1 polymorphisms: gene frequencies and linkage disequilibrium in a population diversity panel. J Thromb Haemost. 2005;3:1511-21. DOI: https://doi.org/10.1111/j.1538-7836.2005.01273.xSomanath PR, Malinin NL, Byzova TV. Cooperation between integrin alphavbeta3 and VEGFR2 in angiogenesis // Angiogenesis. 2009;12(2):177-185. DOI: 10.1007/s10456-009-9141-9Verdoia M, Cassetti E, Schaffer A, et al. Platelet glycoprotein IIIa Leu33Pro gene polymorphism and coronary artery disease: A meta-analysis of cohort studies. Platelets. 2015;26(6):530-535. DOI: https://doi.org/10.3109/09537104.2014.948839Yee DL, Bray PF. Clinical and functional consequences of platelet membrane glycoprotein polymorphisms. Semin Thromb Hemost. 2004;30(5):591-600. DOI: 10.1055/s-в 2004-835679Misra A, Feng Z, Chandran RR, et al. Integrin beta3 regulates clonality and fate of smooth muscle-derived atherosclerotic plaque cells. Nat Commun. 2018;9(1):2073. DOI: https://doi.org/10.1038/s41467-018-04447-7Shoenfeld Y, Harats D, Wick G. Atherosclerosis and Autoimmunity 1st Edition. 2001;2:349.