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Registration Number

0225U004382, (0125U002656) , R & D reports

Title

The role of mitochondrial mechanisms in the development and prevention of cardiovascular dysfunctions in aging

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Вияснення ролі сірководню у реалізації ефектів, які лежать в основі ішемічного прекондиціону-вання, у серці дорослих щурів, та вивчення впливу стимуляції ендогенного синтезу сірководню на механізми, що лежать в основі ішемічного перекондиціонування у серці старих щурів

Head

Sahach Vadym F., Доктор медичних наук

Registration Date

03-12-2025

Organization

Bogomolets Institute of Physiology of the National Academy of Sciences of Ukraine

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The purpose of this project is to establish patterns and features of mitochondrial mechanisms in the development and prevention of cardiovascular disturbances in aging. The study will focus on restoration of mitochondrial function by activating endogenous hydrogen sulfide synthesis to prevent the development of functional changes in the heart and blood vessels in aging. This approach may be particularly relevant for patients with pre-existing cardiovascular disease and endothelial dysfunction.

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It was found that inhibition of H2S-synthesizing enzymes not only exerted a depressant effect on the heart, impaired the rate of myocardial contraction and relaxation (dP/dtmax), increased the tone of coronary vessels, but also abolished the protective effect of ischemic preconditioning. It was shown that administration of a combination of modulators of H2S-synthesizing enzymes, DL-propargylglycine (PAG) and L-cysteine, significantly improved the recovery of function of the isolated heart, increased the efficiency of oxygen utilization by ischemic myocardium in old animals, and partially restored the effect of ischemic preconditioning. It was found that these changes include the expression of genes encoding enzymes for endogenous H2S synthesis, cystathionine-gamma-lyase and 3-mercaptopyruvate-sulfurtransferase, and components of the mitochondrial pore mPTP. According to the results of the study, we were able to: 1) establish the important role of mitochondrial H2S in endogenous mechanisms of cardioprotection, which may become a target for the development of drugs for pathologies of the cardiovascular system; 2) prove the effectiveness of the combination PAG + L-cysteine for increasing myocardial resistance to ischemia during aging; 3) demonstrate some molecular and mitochondrial mechanisms of the protective action of the combination PAG + L-cysteine.

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Ruslan B. Strutynskyi
Oleksandr O. Lisovyi
Yuliia P. Korkach
Nataliia A. Strutynska
Lidiia A. Mys
Iryna Y. Okhai
Vadym F. Sahach
Yulia V. Hoshovska

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2025-12-03