Clinical Physiology of Circulation

Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, President of Bakoulev National Medical Research Center for Cardiovascular Surgery


Influence of polymorphism of the endotheline receptor type A gene(ENDRA rs1801708) and dysfunction of vascular endotheliumon the results of the percutaneous coronary intervention

Authors: Yu.I. Buziashvili, I.V. Koksheneva, S.T. Matskeplishvili, I.A. Inauri, V.Yu. Buziashvili, I.P. Shuvaev, O.M. Sherstyannikova

Company:
Bakoulev National Medical Research Center for Cardiovascular Surgery, Ministry of Health of the Russian Federation, Rublevskoe shosse, 135, Moscow, 121552, Russian Federation

E-mail: Сведения доступны для зарегистрированных пользователей.

DOI: https://doi.org/10.24022/1814-6910-2019-16-3-192-208

UDC: 616.132.2-089.168:611.018.74-008

Link: Clinical Physiology of Blood Circulaiton. 2019; 16 (3): 192-208

Quote as: Buziashvili Yu.I., Koksheneva I.V., Matskeplishvili S.T., Inauri I.A., Buziashvili V.Yu., Shuvaev I.P., Sherstyannikova O.M. Influence of polymorphism of the endotheline receptor type A gene (ENDRA rs1801708) and dysfunction of vascular endothelium on the results of the percutaneous coronary intervention. Clinical Physiology of Circulation. 2019; 16 (3): 192–208 (in Russ.). DOI: 10.24022/1814-6910-2019-16-3-192-208

Received / Accepted:  06.06.2019/02.07.2019

Full text:  

Abstract

Objective. To study the effects of the gene polymorphism of endothelin receptor type A (ENDRA rs1801708) on the course of coronary heart disease (CHD), the incidence of multifocal atherosclerosis, characteristics of coronary lesions and the results of percutaneous coronary interventions (PCI) in patients with CHD.

Material and methods. The study included 84 patients with CHD who had planned PCI. At the beginning of the observation, the average age of the patients was 59.3±2.05 years. The average follow-up was 6.15±0.2 years. Patients underwent genetic testing for the carriage of polymorphic SNP variants of the endothelin type A receptor gene (ENDRA) (rs1801708). A comparison was made of the parameters described above in carriers of different genotypes of ENDRA. To this end, the analysis was carried out in three groups of CHD patients: Group 1 (42 patients) – carriers of the “wild” GG ENDRA genotype rs1801708, Group 2 (34 patients) – carriers of the genotype AG ENDRA rs1801708, Group 3 (8 patients) – carriers of the AA ENDRA rs1801708 genotype.

Results. Analysis of the results of PCI showed that the carriers of the AA ENDRA rs1801708 genotype have significantly worse results of interventional interventions, as compared with the carriers of other ENDRA rs1801708 genotypes. In carriers of the AA genotype, angina return was significantly more frequent in mid-term after the intervention. According to stress echocardiography, their functional performance was significantly worse: the exercise tolerance threshold was lower, a positive stress test result was determined more often, indicating the presence of stress-induced myocardial ischemia and a high risk of adverse cardiovascular events. According to the control coronary angiography, the frequency of detection of stent restenosis and progression of coronary atherosclerosis was higher. The total angiographic index of adverse PCI results (stent restenosis + progression of atherosclerosis + stent thrombosis) was significantly higher in patients with AA genotype carriers: 40% in carriers of the GG genotype, 38% in carriers of the AG genotype, 80% in carriers of the AA genotype. Repeated procedures for myocardial revascularization were significantly more frequently performed on carriers of the AA ENDRA rs1801708 genotype. ENDRA polymorphism rs1801708 affects the severity of endothelial dysfunction that develops after interventional intervention, assessed by the concentration of plasma markers (adhesive VCAM molecule, von Willebrand factor, activity of antithrombin III, protein C, protein S) immediately after PCI and within 1 year after interventional intervention.

Conclusion. The study showed that ENDRA rs1801708 polymorphism is associated with negative results of PCI through the development of a more pronounced dysfunction of the vascular endothelium in response to interventional intervention.

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About Authors

  • Yuriy I. Buziashvili, Dr. Med. Sc., Professor, Academician of the Russian Academy of Sciences, Head of the Clinical-Diagnostic Department; orcid.org/0000-0001-7016-7541
  • Inna V. Koksheneva, Dr. Med. Sc., Senior Researcher; orcid.org/0000-0002-8797-9340
  • Simon T. Matskeplishvili, Dr. Med. Sc., Professor, Corresponding Member of the Russian Academy of Sciences, Chief Researcher
  • Il'ya A. Inauri, Junior Researcher
  • Viktoriya Yu. Buziashvili, Cand. Med. Sc., Junior Researcher; orcid.org/0000-0001-6589-9346
  • Igor' P. Shuvaev, Cand. Med. Sc., Cardiologist; orcid.org/0000-0003-1242-687Х
  • Ol'ga M. Sherstyannikova, Cand. Med. Sc., Researcher; orcid.org/0000-0002-0340-695Х

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