Mitoprotective effect of mesenchymal stem cells-derived conditioned medium in myocardial reperfusion injury of aged rats: role of SIRT-1/PGC-1α/NRF-2 network

Background The aged myocardium experiences various forms of stress that cause reduction of its tolerance to injury induced by ischemia/reperfusion (I/R). Developing effective cardioprotective modalities to prevent the amplification of I/R injury during aging is under focus of investigation. Mesenchy...

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Bibliographic Details
Published in:Molecular biology reports 2023-07, Vol.50 (7), p.5655-5665
Main Authors: Nejati-Koshki, Kazem, Mokhtari, Behnaz, Badalzadeh, Reza, Arabzadeh, AmirAhmad, Mohammadzadeh, Alireza
Format: Article
Language:English
Subjects:
Aging
Animal Anatomy
Animal Biochemistry
Biomedical and Life Sciences
Biosynthesis
GA-binding protein
Histology
Inflammation
Interleukin 6
Ischemia
Life Sciences
Membrane potential
Mesenchymal stem cells
Mitochondria
Morphology
Myocardial infarction
Myocardium
Original Article
Reperfusion
Stem cells
Tumor necrosis factor-α
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Summary:Background The aged myocardium experiences various forms of stress that cause reduction of its tolerance to injury induced by ischemia/reperfusion (I/R). Developing effective cardioprotective modalities to prevent the amplification of I/R injury during aging is under focus of investigation. Mesenchymal stem cells (MSCs) have the ability to regenerate infarcted myocardium mostly by producing multiple secretory factors. This study aimed to explore the mechanisms of mitoprotection by MSCs-conditioned medium (CM) in myocardial I/R injury of aged rats. Methods Male Wistar rats (n = 72, 400–450 g, 22–24 months old) were randomized into groups with/without I/R and/or MSCs-CM treatment. To establish myocardial I/R injury, the method of LAD occlusion and re-opening was employed. MSCs-CM was administered intramyocardially (150 μl) at the onset of reperfusion in recipient group. After 24 h reperfusion, myocardial infarct size, LDH level, mitochondrial functional endpoints, expression of mitochondrial biogenesis-associated genes, and the levels of pro-inflammatory cytokines were evaluated. After 28 days reperfusion, echocardiographic assessment of cardiac function was performed. Results MSCs-CM treatment improved myocardial function and decreased infarct size and LDH level in aged I/R rats ( P  
ISSN:0301-4851
1573-4978
DOI:10.1007/s11033-023-08499-x