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Bolotskaya A.A.

Sechenov First Moscow State Medical University

Kalinin A.P.

Chazov National Medical Research Center of Cardiology;
Lomonosov Moscow State University

Zubkova E.S.

Chazov National Medical Research Center of Cardiology

Ratner E.I.

Chazov National Medical Research Center of Cardiology

Menshikov M.Yu.

Chazov National Medical Research Center of Cardiology

Angiotensin model as a new approach to study of mesenchymal stem cell senescence

Authors:

Bolotskaya A.A., Kalinin A.P., Zubkova E.S., Ratner E.I., Menshikov M.Yu.

More about the authors

Journal: Russian Cardiology Bulletin. 2025;20(2): 20‑26

DOI: 10.17116/Cardiobulletin20252002120

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Table of contents

ANGIOTENSIN MODEL AS A NEW APPROACH TO STUDY OF MESENCHYMAL STEM CELL SENESCENCE
ANGIOTENSIN MODEL AS A NEW APPROACH TO STUDY OF MESENCHYMAL STEM CELL SENESCENCE

To cite this article:

Bolotskaya AA, Kalinin AP, Zubkova ES, Ratner EI, Menshikov MYu. Angiotensin model as a new approach to study of mesenchymal stem cell senescence. Russian Cardiology Bulletin. 2025;20(2):20‑26. (In Russ.)
https://doi.org/10.17116/Cardiobulletin20252002120

Подписка 2026 Кардиологический вестник (Russian Cardiology Bulletin)
МСФ на ЯМ
Использование инфографики авторами научных работ
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Abstract:

BACKGROUND

Aging contributes to pathological changes in tissues aggravating the course of cardiovascular, nervous and other diseases. Senescence of mesenchymal stem cells (MSCs) leading to release of proinflammatory factors contributes to fibrosis. Persistent pathologically high concentration of angiotensin II (ANG) causes aging of various cells, but its effect on senescence of MSCs has not yet been studied.

OBJECTIVE

To develop a model of cellular senescence induced by long-term exposure of MSC culture to angiotensin and to evaluate the possibilities of its pharmacological regulation.

RESULTS

Long-term exposure to ANG reduces MSC proliferation, enhances expression of senescence-associated beta-galactosidase and cell cycle inhibitors, proteins p21 and p53, increases secretion of some factors stimulating migration of inflammatory and immune cells, as well as VEGF. Increased transcription of matrix metalloproteinases MMP1, MMP3 and MMP9 was also detected without changes in transcription of inhibitors (TIMP2 and TIMP3). The angiotensin receptor antagonist telmisartan does not induce expression of senescence markers and does not significantly affect angiotensin-induced secretion. Melatonin with antioxidant effect does not potentiate expression of senescence markers, and in some cases suppresses secretion of angiotensin-inducible factors. At the same time, melatonin is able to enhance secretion of some factors in MSCs without being a pro-senescence factor.

CONCLUSION

Long-term exposure of MSC culture to angiotensin induces appearance of senescence markers, as well as formation of specific senescence-associated secretory phenotype. Potential effects of telmisartan and melatonin on angiotensin-inducible senescence in MSCs allow us to consider these drugs as potential senescence modulators.

Keywords:

mesenchymal stem cells
senescence
angiotensin
telmisartan
melatonin
senescence-associated secretory phenotype

Authors:

Bolotskaya A.A.

Sechenov First Moscow State Medical University

Kalinin A.P.

Chazov National Medical Research Center of Cardiology;
Lomonosov Moscow State University

Zubkova E.S.

Chazov National Medical Research Center of Cardiology

Ratner E.I.

Chazov National Medical Research Center of Cardiology

Menshikov M.Yu.

Chazov National Medical Research Center of Cardiology

Received:

13.11.2024

Accepted:

02.12.2024

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