Morphometric and genetic studies of the mechanisms of damage to the cardiovascular system in Kuzbass miners with dust lung pathology

Abstract

Introduction. The combined impact of unfavorable factors of the production environment in miners leads to the development of associated pathology of the bronchopulmonary and cardiovascular systems, the predisposition to which depends on the individual susceptibility of the body. In this regard, it is important to comprehensively study the pathogenetic mechanisms underlying the formation and course of occupational and work-related diseases for a personalized approach to the diagnosis, prevention and therapy of this pathology. The purpose of this study was to study the mechanisms of damage to the cardiovascular system in miners with dust lung pathology on the basis of morphological and genetic studies. Materials and methods. For genetic studies, venous blood drawing was conducted in 190 Kuzbass miners. The main group included 126 miners of the main professions with the previously proven diagnosis "dust lung pathology", the comparison group consisted of 64 workers without a proven diagnosis working in similar sanitary and hygienic conditions. Morphometric studies were carried out using autopsy material obtained during 80 forensic medical examinations of miners in the Kemerovo region. All the miners were divided into 4 groups depending on their underground work experience. The control group was formed from 20 cases of forensic medical examinations of men who died in road accidents and did not have organ pathology according to the results of autopsies. Results. The study of the autopsy material revealed the presence of morphostructural changes in the vascular walls of the miners’ hearts in the form of hypertrophy of the smooth muscle cells of the medial layers, thickening of the endothelial lining, and the development of fibroplastic changes in the perivascular zones. These changes began to form from the first years of work in the underground conditions and progressed with increasing work experience contributing to the "recalibration" of the heart vessels with the formation of the lumen "obstruction". One of the mechanisms of endothelial damage in miners was a change in the expression of the EDN1 gene, which regulates the synthesis of endothelin-1. The risk and resistance genotypes of the development of dust lung pathology for the rs5370 polymorphism of the EDN1 gene were identified. Morphostructural rearrangement of the endothelium in the combination with its pathological activation contributed to the occurrence of endothelial dysfunction in miners. Conclusions. The conducted studies of the parameters of the vascular endothelium indicate its key role in the pathogenesis of bronchopulmonary and cardiovascular pathology in miners of the main professions. Getting into the body of workers, particles of coal-rock dust lead to morphostructural rearrangement of the cells of the endothelial layer and its pathological activation. The contribution of molecular and genetic mechanisms to the development of occupational lung pathology and associated diseases of the circulatory system in miners is revealed. Ethics. The studies were carried out in compliance with the ethical standards of the Bioethical Committee of the Research Institute for Complex Problems of Hygiene and Occupational Diseases, elaborated on the basis of the Helsinki Declaration of the World Medical Association "Ethical Principles for Conducting Human Scientific Medical Research" as amended in 2013 and the "Rules of Clinical Practice in the Russian Federation" approved by the Order of the Ministry of Health of the Russian Federation No. 266 dated 19.06.2003. All workers were informed about their participation in the molecular-genetic study and gave written consent to carry it out. The research of the dead miners was based on the secondary examination of blocks and ready-made histological micro-preparations of the material of the Bureau for Forensic Medical Expert Examination of the cities of Novokuznetsk, Osinniki, and Prokopyevsk. The study of pathomorphological material was carried out in accordance with the Federal Law of 21.11.2011, No. 323-FZ "On the Fundamentals of Health Protection of Citizens in the Russian Federation", in particular, with Article 67 "Carrying out pathological and anatomical autopsies", Federal Law of 12.01.1996, No. 8-FZ "On burial and funeral business" (Article 5, paragraphs 1, 2), as well as on the basis of the Order of the Ministry of Health of April 29, 1994, No. 82 "On the procedure for conducting pathological and anatomical autopsy" (Annex to the Order of the Ministry of Health and Medical Industry of 29.04.1994 No. 82), the Order of the Ministry of Health of Russia of 24.03.2016. No. 179n "On the rules for conducting pathological and anatomical examinations".