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Information × Registration Number 0224U033111, (0124U002937) , R & D reports Title The role of mitochondrial mechanisms in the development and prevention of cardiovascular dysfunctions in aging. popup.stage_title Оцінка основних показників, що характеризують розвиток мітохондріальної дисфункції у серці старих щурів та в умовах стимуляції ендогенного синтезу сірководню. Вивчення функціонального стану судин, їх редокс-статусу, продукції NO та H2S у старих щурів за умов стимуляції ендогенного синтезу сірководню. Head Sahach Vadym F., Доктор медичних наук Registration Date 18-12-2024 Organization Bogomolets Institute of Physiology of the National Academy of Sciences of Ukraine popup.description1 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. popup.description2  Hydrogen sulfide (H2S) is an important endogenous gaseous molecule in the cardiovascular system, the synthesis of which is provided by two enzymes, cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulfur transferase (3-MPST). With age, the production of this gasotransmitter in heart tissues and, in particular, mitochondria decreases significantly, which weakens its cardioprotective effects. A method for restoring H2S biosynthesis during aging is proposed based on the action of modulators of H2S-synthesizing enzymes DL-propargylglycine (PAG) and L-cysteine. Under conditions of stimulation of endogenous synthesis of hydrogen sulfide in old animals, its mitoprotective effects were revealed due to the inhibition of pore formation during induction of the mitochondrial pore (mitochondrial permeability transition pore, mPTP) by Ca2+ ions against the background of activation of constitutive NO synthesis due to the restoration of mtNOS activity in organelles and the slowing down of the production of reactive oxygen species and lipid peroxidation, which prevented the development of mitochondrial dysfunction. Stimulation of endogenous synthesis of H2S in old rats effectively restored vasodilatory vascular reactions in them, which are known to decrease with age. The mechanism of the vasoprotective effect was the restoration of H2S production due to increased expression of H2S-synthesizing enzyme genes, maintenance of redox status, increased activity and expression of endothelial NO synthase and inhibition of inducible NO synthesis, as well as activation of the expression of ATP-sensitive potassium channel subunits of cell membranes. Our results clearly demonstrate that restoration of endogenous H2S synthesis and its signaling is important for maintaining mitochondrial function and may contribute to the prevention and treatment of cardiovascular disorders in aging. Product Description popup.authors Hoshovska Yuliia V. Denysova Maiia V. Korkach Yuliia P. Mys Lidiia A. Okhai Iryna Yu. Sahach Vadym F. Strutynska Nataliia A. Strutynskyi Ruslan B. popup.nrat_date 2024-12-18 Close