Proteolysis/antiproteolysis system in apparently healthy men and women of different ages
- Authors: Yushchuk V.N.1, Chepurnova N.S.1, Markelova E.V.1, Ermolitskaya M.Z.2, Savchenko A.Y.3, Zakharov I.N.3, Andrushchenko K.A.1, Barabash P.V.1, Xing Y.J.1, Meshcheryakova D.A.1, Plekhova N.G.1
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Affiliations:
- Pacific State Medical University
- Institute of Automation and Control Processes
- Far Eastern Federal University
- Issue: Vol 28, No 3 (2024): PHYSIOLOGY. EXPERIMENTAL PHYSIOLOGY
- Pages: 340-352
- Section: PHYSIOLOGY. EXPERIMENTAL PHYSIOLOGY
- URL: https://journals.rudn.ru/medicine/article/view/40854
- DOI: https://doi.org/10.22363/2313-0245-2024-28-3-340-352
- EDN: https://elibrary.ru/CRURBE
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Abstract
Relevance. Aging is a natural biological process of a retrograde nature, during which there is an imbalance of all systems, including the matrix metalloproteinase (MMP) system and tissue inhibitors of matrix metalloproteinases (TIMP). And vascular aging is associated with functional and structural changes primarily in the arterial vasculature with age. Aging may be a trigger factor for pathological changes in the endothelium. The molecular mechanisms underlying the process of vascular endothelial dysfunction include increased expression and activation of matrix metalloproteinases, the concentration of which changes with aging. Numerous studies report the role of MMP-1, –2, –9, –12 in the pathogenesis of premature aging of the endothelium; they initiate cell apoptosis, which contributes to increased permeability, but there are no studies in which all age categories of both men and women were analyzed, not burdened by somatic pathology. This study examines the features of the proteolysis/antiproteolysis system in apparently healthy people of different ages and genders. Materials and Methods. As part of the pilot study, 347 apparently healthy people took part (226 women and 121 men, divided by age, according to the WHO classification), who underwent the first stage of clinical examination at the State Budgetary Institution “Consultative and Diagnostic Center of the Mountains. Yuzhno-Sakhalinsk”, in which the level of MMP and TIMP in the blood serum was determined by solid-phase ELISA, ng/ml. Statistical processing of the research results was carried out using the IBM SPSS Statistics Version 25.0 software package. Results and Discussion. Changes in the proteolysis/antiproteolysis system were determined in both a group of men and women of different ages, which can be characterized as not pathological, but close to such. It was found that in men aged 60-74 years, discoordinated work of matrix metalloproteinases and their inhibitors was recorded in the direction of enhancing the profibrosing effect, and in women in the same age category, the exact opposite component was identified — anti-fibrosing. Conclusion. The current development has demonstrated the influence of age and genetic resources on the system of matrix metalloproteinases and their tissue inhibitors, in addition, a special age group has been identified — the elderly group, which requires protection of the vascular system in order to monitor the impaired proteolysis/antiproteolysis system.
About the authors
Vladimir N. Yushchuk
Pacific State Medical University
Email: dr.cns@yandex.ru
SPIN-code: 7096-1850
Vladivostok, Russian Federation
Natalia S. Chepurnova
Pacific State Medical University
Email: dr.cns@yandex.ru
ORCID iD: 0000-0001-6642-1332
SPIN-code: 6726-8523
Vladivostok, Russian Federation
Elena V. Markelova
Pacific State Medical University
Email: dr.cns@yandex.ru
ORCID iD: 0000-0001-5846-851X
SPIN-code: 3661-5026
Vladivostok, Russian Federation
Marina Z. Ermolitskaya
Institute of Automation and Control Processes
Email: dr.cns@yandex.ru
ORCID iD: 0000-0003-2588-102X
SPIN-code: 9197-4028
Vladivostok, Russian Federation
Anastacia Yu. Savchenko
Far Eastern Federal University
Email: dr.cns@yandex.ru
Vladivostok, Russian Federation
Ivan N. Zakharov
Far Eastern Federal University
Email: dr.cns@yandex.ru
Vladivostok, Russian Federation
Ksenia A. Andrushchenko
Pacific State Medical University
Author for correspondence.
Email: dr.cns@yandex.ru
ORCID iD: 0009-0005-0942-8075
Vladivostok, Russian Federation
Polina V. Barabash
Pacific State Medical University
Email: dr.cns@yandex.ru
ORCID iD: 0009-0006-5548-3451
Vladivostok, Russian Federation
Yang Jia Xing
Pacific State Medical University
Email: dr.cns@yandex.ru
ORCID iD: 0009-0008-5962-2118
Vladivostok, Russian Federation
Daria A. Meshcheryakova
Pacific State Medical University
Email: dr.cns@yandex.ru
ORCID iD: 0009-0003-6410-8248
Vladivostok, Russian Federation
Natalia G. Plekhova
Pacific State Medical University
Email: dr.cns@yandex.ru
ORCID iD: 0000-0002-8701-7213
SPIN-code: 2685-9578
Vladivostok, Russian Federation
References
- Stakhneva EM, Kashtanova EV, Polonskaya Ya V. Mechanisms of vascular aging. Bjulleten’ sibirskoj mediciny. 2022;21(2):186-194. (In Russian).
- Iannarelli NJ, MacNeil AJ, Dempster KS, Wade TJ [et al.] Serum MMP-3 and its association with central arterial stiffness among young adults is moderated by smoking and BMI. Physiology Report. 2021;9(11): e14920.
- Simões G, Pereira T, Caseiro A. Matrix metaloproteinases in vascular pathology. Microvascular Research. 2022;143:104398.
- Stabouli S, Kotsis V, Maliachova O, Printza N. Matrix metalloproteinase -2, -9 and arterial stiffness in children and adolescents: The role of chronic kidney disease, diabetes, and hypertension. International Journal of Cardiology Hypertension. 2020;4:100025.
- Yabluchanskiy A, Ma Y, Iyer RP, Hall ME. Matrix Metalloproteinase-9: Many Shades of Function in Cardiovascular Disease. Physiology. 2013;28:391-403.
- Knox A. Arterial Aging, Metalloproteinase Regulation, and the Potential of Resistance Exercise. Current Cardiology Reviews. 2018;14(4):227-232.
- Wang X, Khalil RA.Matrix metalloproteinases, vascular remodeling, and vascular disease. Advances in Pharmacology. 2018;8:241-330.
- Grzhibovsky AM, Ungureanu TN. Analysis of biomedical data using the statistical software package SPSS: textbook. Arkhangelsk: Publishing House of the Northern State Medical University, 2017. - 293 p. (In Russian).
- Mudrov VA. Algorithms for statistical analysis of qualitative features in biomedical research using the SPSS software package. JeNI Zabajkal’skij medicinskij vestnik. 2020;1:151-163. (In Russian).
- Knysh SV, Chepurnova NS, Birko ON, Baibarina EV, Kudinov AA, Pirozhinskaya AA. Study of indicators of the system of metalloproteinases and their tissue inhibitors in the blood serum of patients of different age groups. Rossijskij allergologicheskij zhurnal. 2019;16(1):72-74. (In Russian).
- Bonnema DD, Webb CS, Pennington WR, Stroud RE, Leonardi AE, Clark LL, McClure CD, Finklea L, Spinale FG, Zile MR. Effects of age on plasma matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs). Journal of Cardiac Failure. 2007;13(7):530-540. doi: 10.1016/j.cardfail.2007.04.010
- Cancemi P, Aiello A, Accardi G, Caldarella R, Candore G, Caruso C, Ciaccio M, Cristaldi L, Di Gaudio F, Siino V, Vasto S. The Role of Matrix Metalloproteinases (MMP-2 and MMP-9) in Ageing and Longevity: Focus on Sicilian Long-Living Individuals (LLIs). Mediators Inflammation. 2020; P:1-11. doi: 10.1155/2020/8635158
- Freitas-Rodríguez S, Folgueras AR, López-Otín C. The role of matrix metalloproteinases in aging: Tissue remodeling and beyond. Acta Molecular Cell Research. 2017;1864:2015-2025. doi: 10.1016/j.bbamcr.2017.05.007
- Xiao P, Zhang Y, Zeng Y. Impaired angiogenesis in ageing: the central role of the extracellular matrix. J. Transl. Med. 2023;21:457. doi: 10.1186/s12967-023-04315-z
- Jacob MP. Extracellular matrix remodeling and matrix metalloproteinases in the vascular wall during aging and in pathological conditions. Biomed Pharmacother. 2003; 57(5-6):195-202. doi: 10.1016/s0753-3322(03)00065-9
- Dworatzek E, Baczko I, Kararigas G. Effects of aging on cardiac extracellular matrix in men and women. Proteomics Clin Appl. 2016;10(1):84-91. doi: 10.1002/prca.201500031
- Kremastiotis G, Handa I, Jackson C, George S, Johnson J. Disparate effects of MMP and TIMP modulation on coronary atherosclerosis and associated myocardial fibrosis. Sci Rep. 2021;30.11(1):23081. doi: 10.1038/s41598-021-02508-4
- Cabral-Pacheco GA., Garza-Veloz I, Castruita-De la Rosa C, Ramirez-Acuña JM, Perez-Romero BA, Guerrero-Rodriguez JF, Martinez-Avila N, Martinez-Fierro ML. The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases. Int J Mol Sci. 2020;20;21(24):9739. doi: 10.3390/ijms21249739
- Kolomeychuk SN, Korneva VA, Ilyukha VV, Kuznetsova AS, Kuznetsova T Yu. Study of polymorphic variants of the matrix metalloproteinase 3 (MMP-3) gene as a marker of the risk of developing arterial hypertension and coronary heart disease in the population of the Republic of Karelia. Journal of Biomedical Technologies. 2014;2:10-16. (In Russian). doi: 10.15393/j6.art.2014.320220
- Britton R, Wasley T, Harish R, Holz C, Hall J, Yee DC, Melton Witt J, Booth EA, Braithwaite S, Czirr E, Kerrisk CM. Noncanonical Activity of Tissue Inhibitor of Metalloproteinases 2 (TIMP-2) Improves Cognition and Synapse Density in Aging. eNeuro. 2023;10(6):1-23.2023. doi: 10.1523/ENEURO.0031-23.2023
- Litvinova MS, Khaisheva LA, Kuts EI. Relationship between matrix metalloproteinase-9 and its inhibitor with parameters of 24-hour blood pressure monitoring in patients with resistant arterial hypertension. Rossijskij kardiologicheskij zhurnal. 2022;6:131-133. (In Russian).