Features of the immune and genetic status of chemical industry workers with pathology of the cardiovascular system

Introduction. Working in a chemical production environment is associated with a high risk of developing cardiovascular diseases (CVD) in workers.

The study aims to consider the characteristics of the immune and genetic status of workers with cardiovascular pathology engaged in the production of mineral fertilizers.

Materials and methods. The observation group included 74 people (with a history of CVD). The comparison group included 85 people (conditionally healthy, with no history of CVD). The work used immunological methods: allergosorbent test with an enzyme label, membrane immunofluorescence on a flow cytometer, ELISA. To statistically process the results of the study, the authors used the following criteria: Student's t-test, Mann–Whitney U-test, relative risk index (RR), odds ratio (OR) and 95% confidence interval (CI). The significance of the differences was considered significant at p<0.05.

Results. The observation group had elevated levels of IgG specific to N-nitrosodimethylamine (RR=1.10; 95% CI=0.93–1.29), VEGF (RR=1.72; 95% CI=0.64–4.61), CD304⁺ (NRP1) (RR=1.76; 95% CI=1.04–2.97) and Notch 1 receptor (RR=1.89; 95% CI=1.05–3.39). Comparative assessment of frequency of alleles and genotypes of the endothelial NO-synthase gene eNOS Glu298Asp (rs1799983) revealed authentically 10% higher frequency of the G allele (OR=2.53 (CI=1.23–5.22), RR=1.28 (CI=1.06–1.55), р≤0.05) and 1.67 times higher frequency of the GG genotype (OR=3.72 (CI=1.49–9.29), р≤0.05) in the observation group.

Limitations. Limitations of the study are associated with a limited sample used as the observation group.

Conclusion. Established elevated expression of cell differentiation clusters of neuropilin-1 CD 304⁺ (RR=1.76; 95% CI=1.04–2.97) and transmembrane receptor protein Notch 1 (RR=1.89; 95% CI=1.05–3.93) against higher frequency of the G allele and GG genotype of the eNOS Glu298Asp gene increases likelihood of changes in endothelium, impaired vascular wall permeability and development of cardiovascular pathology in conditions of biocontamination with nitrosamines among workers working in the production of mineral fertilizers.

Ethics. The work was carried out in accordance with the principles of the Helsinki Declaration. The protocol and design of the study were approved by the local committee of the Federal Research Foundation "Federal Scientific Center for Medical and Preventive Technologies for Public Health Risk Management" dated 03/13/2024, Protocol No. 2.

Contributions:
Zaitseva N.V. — concept and design of the study;
Chelakova Yu.A. — data collection and processing, text writing, editing;
Dolgikh O.V. — concept and design of research, editing.

Funding. The study had no funding.

Conflict of interest. The authors declare no conflict of interest.

Received: 18.04.2025 / Accepted: 15.07.2025 / Published: 05.09.2025

1. Artemov A.V., Brуkin A.V., Ivanov M.N. et al. Analysis of development strategy of pctrochemkhal industry till 2015. Rossiyskiy khimicheskiy zhurnal. 2008; 4: 4–14. https://elibrary.ru/jtfejx (in Russian).

2. Mekhantyeva L.E. Effect of fertilizer industries of female reproductive health. Sistemnyy analiz i upravlenie v biomeditsinskikh sistemakh. 2007; 6; 2: 389–394. https://elibrary.ru/jvhpbb (in Russian).

3. Petukhova Ya.Yu. Increasing the level of industrial safety in the workshop for the production of complex mineral fertilizers. Vestnik nauki. 2023; 5(62): 1210–1217. https://elibrary.ru/avrocb (in Russian).

4. Gimaeva Z.F., Bakirov A.B., Kuzmina L.P., et al. Diagnostic significance of lipid profile indicators for assessing chemical workers’ cardiovascular risk. Meditsina truda i promyshlennaya ekologiya. 2022; 61(1): 19–28. https://doi.org/10.31089/1026-9428-2022-62-1-19-28 https://elibrary.ru/xpuuqn (in Russian).

5. Shlyakhto E.V. ed. Cardiology. National guidelines (short edition). M.: GEOTAR-Media; 2018. https://elibrary.ru/zrqfqz (in Russian).

6. Izmerov N.F., Boukhtiarov I.V., Prokopenko L.V. et al. Protecting health of workers and predictive preventive personified medicine. Meditsina truda i promyshlennaya ekologiya. 2013; 6: 7–12. https://elibrary.ru/qiutvp (in Russian).

7. Sgroi M., Roccaro P., Oelker G.L., Snyder S.A. N-nitrosodimethylamine formation upon ozonation and identification of precursors source in a municipal wastewater treatment plant. Environ. Sci. Technol. 2014; 48(17): 10308-10315. https://doi.org/10.1021/es5011658

8. Arranz N., Haza A.I., Garcia A. et al. Protective effect of vitamin C towards N-nitrosamine-induced DNA damage in the single-cell gel electrophoresis (SCGE)/HepG2 assay. Toxicol. In Vitro. 2007; 21(7): 1311–1317. https://doi.org/10.1016/j.tiv.2007.03.015

9. Griendling K.K., FitzGerald G.A. Oxidative stress and cardiovascular injury: Part I: basic mechanisms and in vivo monitoring of ROS. Circulation. 2003; 108(16): 1912–1916. https://doi.org/10.1161/01.CIR.0000093660.86242.BB

10. Harrison D., Griendling K.K., Landmesser U., et al. Role of oxidative stress in atherosclerosis. The American Journal of Cardiology. 2003; 91(3): 7A–11A. https://doi.org/10.1016/s0002-9149(02)03144-2

11. Inoue N. Stress and atherosclerotic cardiovascular disease. Journal of Atherosclerosis and Thrombosis. 2014; 21(5): 391–401. https://doi.org/10.5551/jat.21709

12. Kazakova O.A., Yaroma A.V., Dolgikh O.V. Contamination of biomedia with N-nitrosamines as a factor in the development of disorders of the immune status in schoolchildren with dyspepsia under conditions of altered polymorphism of candidate genes. Gigiena i sanitariya. 2022; 101(11): 1362–1367. https://doi.org/10.47470/0016-9900-2022-101-11-1362-1367 https://elibrary.ru/hypgly (in Russian).

13. Zaitseva N.V., Zemlyanova M.A., Alekseyev V.B., Scherbina S.G. Cytogenetic markers and hygienic criteria for assessment of chromosomal abnormalities in population and workers exposed to environmental and workplace hazards. Perm': Knizhnyy format; 2013. https://elibrary.ru/wvlnox (in Russian).

14. Balatskii A.V., Andreenko E.Iu., Samokhodskaia L.M. et al. Endothelial NO synthase and connexin 37 gene polymorphisms as a risk factor for myocardial infarction in subjects without a history of coronary artery disease. Terapevticheskiy arkhiv. 2013; 85(9): 18–22. https://elibrary.ru/pzgzli (in Russian).

15. Tretyakov S.V., Shilov S.N. Popova A.A. General patterns in the response of the cardiovascular system to occupational factors. Mezhdunarodnyy nauchno-issledovatel'skiy zhurnal. 2023; 7(133). https://doi.org/10.23670/IRJ.2023.133.45 https://elibrary.ru/jqsxef (in Russian).

16. Trape J.C., Morales R., Molina X., et al. Vascular endothelial growth factor serum concentrations in hypercholesterolemic patients. Scand. J. Clin. Lab. Invest. 2006; 66(3): 261–267. https://doi.org/10.1080/00365510600564949

17. Suzuki H., Murakami M., Shoji M., et al. Hepatocyte growth factor and vascular endothelial growth factor in ischemic heart di-sease. Coron. Artery Dis. 2003; 14(4): 301–307. https://doi.org/10.1097/01.mca.0000073431.02845.a1

18. Rekalov D.G. Peculiarities of the metabolism of vascular growth factors in patients with hypertension. Materialy nauk.-prakt. konf. z mizhnar. uchastju «Diagnostyka i likuvannja urazhennja sercja ta nyrok pry arterial'nij gipertenzii'». 2004: 83–84 (in Ukrainian).

19. Zhukova A.G., Kazitskaya A.S., Yadykina T.K. et al. Polymorphism of HIF-1A (rs11549465) and VEGFA (rs2010963) genes and the immune status in the dust lung pathology miners working at the coal enterprises in the South of Kuzbass. Gigiena i sanitariya. 2021; 100(7): 683–687. https://doi.org/10.47470/0016-9900-2021-100-7-683-687 (in Russian).

20. Jarvis A., Allerston Ch.K., Jia H., et al. Small molecule inhibitors of the neuropilin-1 vascular endothelial growth factor A (VEGF-A) interaction. J. Med. Chem. 2010; 53(5): 2215–26. https://doi.org/10.1021/jm901755g

21. Pellet-Many C., Mehta V., Fields L., et al. Neuropilins 1 and 2 mediate neointimal hyperplasia and re-endothelialization following arterial injury. Cardiovasc. Res. 2015; 108(2): 288–98. https://doi.org/10.1093/cvr/cvv229

22. Domenga V., Fardoux P., Lacombe P., et al. Notch3 is required for arterial identity and maturation of vascular smooth muscle cells. Genes Dev. 2004; 18: 2730–2735. https://clck.ru/3NBJKs

23. Kopan R., Ilagan M.X. The canonical Notch signaling pathway: unfolding the activation mechanism. Cell. 2009; 137: 216–233. https://doi.org/10.1016/j.cell.2009.03.045

24. Andersson E.R., Sandberg R., Lendahl U. Notch signaling: simplicity in design, versatility in function. Development. 2011; 138: 3593–3612. https://doi.org/10.1242/dev.063610

25. Bray S.J. Notch signalling in context. Nat. Rev. Mol. Cell Biol. 2016; 17: 722. https://doi.org/10.1038/nrm.2016.94

26. Roca C., Adams R.H. Regulation of vascular morphogenesis by Notch signaling. Genes & Development. 2007; 21(20): 2511–2524. https://clck.ru/3NBJV8

27. Gridley T. Notch signaling in vascular development and physiology. Development. 2007; 134(15): 2709–2718. https://doi.org/10.1242/dev.004184

28. Ridgway, J., Zhang G., Wu Y. et al. Inhibition of Dll4 signaling inhibits tumor growth by deregulating angiogenesis. Nature. 2006; 444(7122): 1083–1087. https://doi.org/10.1038/nature05313

29. Neufeld G., Kessler O. The semaphorins: versatile regulators of tumor progression and tumor angiogenesis. Nat. Rev. Cancer. 2008; 8: 632–645. https://doi.org/10.1038/nrc2404

30. Uniewicz K.A., Cross M.J., Fernig D.G. Exogenous recombinant dimeric neuropilin-1 is sufficient to drive angiogenesis. J Biol Chem. 2011; 286(1): 12–23. https://doi.org/10.1074/jbc.M110.190801

31. Arutyunyan I.V., Kananykhina E.Y., Makarov A.V. Role of VEGF-A165 receptors in angiogenesis. Kletochnaya transplantologiya i tkanevaya inzheneriya. 2013; 8(1): 12–18. https://elibrary.ru/qakumv (in Russian).