Morpho-Functional Features of The Local Renin-Angiotensin-Aldosterone System of the Uterine Mucosa in Conditions of Uterus Precancer and Neoplastic Diseases
https://doi.org/10.52420/umj.25.1.29
EDN: HDOGWE
Abstract
Introduction. Interest in the renin-angiotensin-aldosterone system (RAAS) is driven by the need to develop and make available effective pharmacotherapy aimed at correcting cardiovascular diseases. However, endometrial elements of reproductive-aged patients also express all RAAS components responsible for stimulating angiogenesis, proliferation, and cell migration in the normal endometrium. When activated and overexpressed, the RAAS can promote abnormal cell proliferation and the spread of atypical cells, which is characteristic of endometrial carcinomas. Literary data on this topic are scarce and contradictory, so studying the specific features of local RAAS function in precancerous and malignant endometrial pathology is relevant.
The purpose of the study is to characterize the specific features of the local uterine RAAS in various types of glandular hyperplasia and endometrial carcinoma in a comparative perspective.
Materials and methods. This study involved a retrospective, non-randomized, single-stage analysis of uterine mucosal biopsies from patients with endometrial precancerous and cancerous conditions using histological and immunohistochemical methods. The results were then analyzed using nonparametric statistical methods.
Results. Statistically significant levels of angiotensin-converting enzyme 2 (ACE2) and progesterone expression were found, characteristic of the normal endometrium, the uterine mucosa with hyperplasia, and endometrioid adenocarcinoma. These results correlate with published data, although the modulation of ACE2 expression by progesterone requires further detailed study.
Conclusion. The results of this study can serve as a basis for the development of software algorithms for personalized care of patients with precancerous and neoplastic diseases.
About the Authors
A. V. Zatvornitskaya
South Ural State Medical University
Russian Federation
Competing Interests:
Russian Federation
Alexandra V. Zatvornitskaya — Candidate of Sciences (Medicine), Assistant of the Department of Pathological Anatomy and Forensic Medicine named after professor V. L. Kovalenko
Chelyabinsk
Competing Interests:
Alexandra V. Zatvornitskaya declares the absence of obvious or potential conflict of interest.
E. L. Kazachkov
South Ural State Medical University
Russian Federation
Competing Interests:
Russian Federation
Evgeniy L. Kazachkov — Doctor of Sciences (Medicine), Professor, Head of the Department of Pathological Anatomy and Forensic Medicine named after professor V. L. Kovalenko
Chelyabinsk
Competing Interests:
Evgeniy L. Kazachkov are editorial board member of Ural Medical Journal, and he did not participate in reviewing the material or making a decision about its publication.
E. A. Kazachkova
South Ural State Medical University
Russian Federation
Competing Interests:
Russian Federation
Ella A. Kazachkova — Doctor of Sciences (Medicine), Professor, Professor of the Department of Obstetrics and Gynecology
Chelyabinsk
Competing Interests:
Ella A. Kazachkova are editorial board member of Ural Medical Journal, and she did not participate in reviewing the material or making a decision about its publication.
References
1. Aganezova NV, Aganezov SS, Gogichashvili KE. Characteristics of endometrial receptivity in women with different endometrial thickness. Obstetrics, Gynecology and Reproduction. 2022;16(2):108–121. (In Russ.). DOI: https://doi.org/10.17749/2313-7347/ob.gyn.rep.2022.303.
2. Hassani B, Attar Z. Firouzabadi, N. The renin-angiotensin-aldosterone system (RAAS) signaling pathways and cancer: Foes versus allies. Cancer Cell International. 2023;23(1):254. DOI: https://doi.org/10.1186/s12935-023-03080-9.
3. Casalechi M, Dela Cruz C, Lima LC, Maciel LP, Pereira VM, Reis FM. Angiotensin peptides in the non-gravid uterus: Paracrine actions beyond circulation. Peptides. 2018;101:145–149. DOI: https://doi.org/10.1016/ j.peptides.2018.01.012.
4. Khan NA, Elsori D, Rashid G, Tamanna S, Chakraborty A, Farooqi A, et al. Unraveling the relationship between the renin-angiotensin system and endometrial cancer: A comprehensive review. Frontiers in Oncology. 2023;13:1235418. DOI: https://doi.org/10.3389/fonc.2023.1235418.
5. Bankhead P, Loughrey MB, Fernández JA, Dombrowski Y, McArt DG, Dunne PD, et al. QuPath: Open source software for digital pathology image analysis. Scientific Reports. 2017;7:16878. DOI: https://doi.org/10.1038/s41598-017-17204-5.
6. Rogaczewski P, Janiak M, Borowczak J, Szylberg Ł. PCMT1 as a prognostic marker in breast cancer. Clinical and Translational Oncology. 2025;27(4):1558–1568. DOI: https://doi.org/10.1007/s12094-024-03695-y.
7. Gerasimov AN, Morozova NI. Parametric and nonparametric methods in medical statistics. Epidemiology and Vaccine Prevention. 2015;14(5):6–12. (In Russ.). DOI: https://doi.org/10.31631/2073-3046-2015-14-5-6-12.
8. Garcia-Garduño TC, Padilla-Gutierrez JR, Cambrón-Mora D, Valle Y. RAAS: A convergent player in ischemic heart failure and cancer. International Journal of Molecular Sciences. 2021;22(13):7106. DOI: https://doi.org/10.3390/ijms22137106.
9. Rachow T, Schiffl H, Lang SM. Risk of lung cancer and renin-angiotensin blockade: A concise review. Journal of Cancer Research and Clinical Oncology. 2021;147(1):195–204. DOI: https://doi.org/10.1007/s00432-020-03445-x.
10. Valentini A, Heilmann RM, Kühne A, Biagini L, De Bellis D, Rossi G. The renin-angiotensin-aldosterone system (RAAS): Beyond cardiovascular regulation. Veterinary Sciences. 2025;12(8):777. DOI: https://doi.org/10.3390/vetsci12080777.
11. Shestakova MV. The role of the tissue renin-angiotensin-aldosterone system in the development of metabolic syndrome, diabetes mellitus and itsvascular complications. Diabetes mellitus. 2010;13(3):14–19. (In Russ.). DOI: https://doi.org/10.14341/2072-0351-5481.
12. Zheng MH, Li FXZ, Xu F, Lin X, Wang Y, Xu QS, et al. The interplay between the renin-angiotensinaldosterone system and parathyroid hormone. Frontiers in Endocrinology. 2020;11:539. DOI: https://doi.org/10.3389/fendo.2020.00539.
13. Caputo I, Bertoldi G, Driussi G, Cacciapuoti M, Calò LA. The RAAS goodfellas in cardiovascular system. Journal of Clinical Medicine. 2023;12(21):6873. DOI: https://doi.org/10.3390/jcm12216873.
14. Gutsol LO, Egorova IE. The influence of tissue angiotensins on elements of the cardiovascular system (lecture). Baikal Medical Journal. 2024;3(2):71–81. (In Russ.). DOI: https://doi.org/10.57256/2949-0715-2024-2-71-81.
15. Karlovich NV, Mokhort TV, Volchek YA. Renin-angiotensin-aldosterone system: Traditional function and pleiotropic effects of regulation of phosphorus-calcium metabolism. Medical news. 2021;(10):22–26. (In Russ.). EDN: https://elibrary.ru/TGHHEC.
16. Zhang X, Zhang Y, Zhang L, Qin C. Overexpression of ACE2 ameliorates Aβ-induced blood-brain barrier damage and angiogenesis by inhibiting NF-κB/VEGF/VEGFR2 pathway. Animal Models and Experimental Medicine. 2023;6(3):237–244. DOI: https://doi.org/10.1002/ame2.12324. Erratum in: Animal Models and Experimental Medicine. 2024;7(6):966–967. DOI: https://doi.org/10.1002/ame2.12489.
17. Jiang Z, Wang Y, Zhao X, Cui H, Han M, Ren X, et al. Obesity and chronic kidney disease. American Journal of Physiology. Endocrinology and Metabolism. 2023;324(1):E24–E41. DOI: https://doi.org/10.1152/ajpendo.00179.2022.
18. Pang Z, Korpela R, Vapaatalo H. Local aldosterone release and CYP11B2 expression in response to angiotensin peptides, glucose, and potassium — an ex vivo study on murine colon. Journal of Physiology and Pharmacology. 2024;75(2):185–194. DOI: https://doi.org/10.26402/jpp.2024.2.07.
19. Molina-Van den Bosch M, Jacobs-Cachá C, Vergara A, Serón D, Soler MJ. El rol del sistema renina angiotensina a nivel cerebral [The renin-angiotensin system and the brain]. Hipertensión y Riesgo Vascular. 2021;38(3):125–132. (In Span.). DOI: https://doi.org/10.1016/j.hipert.2020.12.001.
20. Shabanian S, Khazaie M, Ferns GA, Arjmand MH. Local renin-angiotensin system molecular mechanisms in intrauterine adhesions formation following gynecological operations, new strategy for novel treatment. Journal of Obstetrics and Gynaecology. 2022;42(6):1613–1618. DOI: https://doi.org/10.1080/01443615.2022.2036972.
21. Li SY, Song Z, Yan YP, Li B, Song MJ, Liu YF, et al. Aldosterone from endometrial glands is benefit for human decidualization. Cell Death & Disease. 2020;11(8):679. DOI: https://doi.org/10.1038/s41419-020-02844-9.
22. Liu Y, Hao H, Lan T, Jia R, Cao M, Zhou L, et al. Physiological and pathological roles of Ang II and Ang- (1–7) in the female reproductive system. Frontiers in Endocrinology. 2022;13:1080285. DOI: https://doi.org/10.3389/fendo.2022.1080285.
23. Jing Y, Run-Qian L, Hao-Ran W, Hao-Ran C, Ya-Bin L, Yang G, et al. Potential influence of COVID-19/ACE2 on the female reproductive system. Molecular Human Reproduction. 2020;26(6):367–373. DOI: https://doi.org/10.1093/molehr/gaaa030.
24. Zhao S, Sun W, Jiang P. Role of the ACE2/Ang-(1–7)/Mas axis in glucose metabolism. Reviews in Cardiovascular Medicine. 2021;22(3):769–777. DOI: https://doi.org/10.31083/j.rcm2203083.
25. Cree IA, White VA, Indave BI, Lokuhetti D. Revising the WHO classification: Female genital tract tumours. Histopathology. 2020;76(1):151–156. DOI: https://doi.org/10.1111/his.13977.
26. Ahmed A, Li XF, Shams M, Gregory J, Rollason T, Barnes NM, et al. Localization of the angiotensin II and its receptor subtype expression in human endometrium and identification of a novel high-affinity angiotensin II binding site. The Journal of Clinical Investigation. 1995;96(2):848–857. DOI: https://doi.org/10.1172/ JCI118131.
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For citations:
Zatvornitskaya AV, Kazachkov EL, Kazachkova EA. Morpho-Functional Features of The Local Renin-Angiotensin-Aldosterone System of the Uterine Mucosa in Conditions of Uterus Precancer and Neoplastic Diseases. Ural Medical Journal. 2026;25(1):29–41. (In Russ.) https://doi.org/10.52420/umj.25.1.29. EDN: HDOGWE
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