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.
Aging
Cardioprotection
Conditioned medium
Mesenchymal stem cells
Mitoprotection
Myocardial reperfusion injury
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
received:
01
12
2022
accepted:
28
04
2023
medline:
26
6
2023
pubmed:
18
5
2023
entrez:
18
5
2023
Statut:
ppublish
Résumé
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. 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. MSCs-CM treatment improved myocardial function and decreased infarct size and LDH level in aged I/R rats (P < .05 to P < .001). It also decreased mitochondrial ROS formation, enhanced mitochondrial membrane potential and ATP content, upregulated mitochondrial biogenesis-related genes including SIRT-1, PGC-1α, and NRF-2, and lessened TNF-α, IL-1β, and IL-6 levels (P < .05 to P < .01). MSCs-CM treatment attenuated myocardial I/R injury in aged rats, in part by improving mitochondrial function and biogenesis and restraining inflammatory reaction. the upregulation of SIRT-1/PGC-1α/NRF-2 profiles is a possible target for the mitoprotective effects of MSCs-CM following I/R injury during aging.
Sections du résumé
BACKGROUND
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
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
RESULTS
MSCs-CM treatment improved myocardial function and decreased infarct size and LDH level in aged I/R rats (P < .05 to P < .001). It also decreased mitochondrial ROS formation, enhanced mitochondrial membrane potential and ATP content, upregulated mitochondrial biogenesis-related genes including SIRT-1, PGC-1α, and NRF-2, and lessened TNF-α, IL-1β, and IL-6 levels (P < .05 to P < .01).
CONCLUSIONS
CONCLUSIONS
MSCs-CM treatment attenuated myocardial I/R injury in aged rats, in part by improving mitochondrial function and biogenesis and restraining inflammatory reaction. the upregulation of SIRT-1/PGC-1α/NRF-2 profiles is a possible target for the mitoprotective effects of MSCs-CM following I/R injury during aging.
Identifiants
pubmed: 37199864
doi: 10.1007/s11033-023-08499-x
pii: 10.1007/s11033-023-08499-x
doi:
Substances chimiques
Culture Media, Conditioned
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5655-5665Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature B.V.
Références
Gunata M, Parlakpinar H (2021) A review of myocardial ischaemia/reperfusion injury: pathophysiology, experimental models, biomarkers, genetics and pharmacological treatment. Cell Biochem Funct 39(2):190–217
doi: 10.1002/cbf.3587
pubmed: 32892450
Valikeserlis I, Athanasiou A-A, Stakos D (2021) Cellular mechanisms and pathways in myocardial reperfusion injury. Coron Artery Dis 32(6):567–577
doi: 10.1097/MCA.0000000000000997
pubmed: 33471478
Chen C-L et al (2022) Mitochondrial redox regulation and myocardial ischemia-reperfusion injury. Am J Physiol Cell Physiol 322(1):C12–C23
doi: 10.1152/ajpcell.00131.2021
pubmed: 34757853
Lecour S et al (2021) IMproving preclinical assessment of cardioprotective therapies (IMPACT) criteria: Guidelines of the EU-CARDIOPROTECTION COST action. Basic Res Cardiol 116(1):1–8
doi: 10.1007/s00395-021-00893-5
Kleinbongard P et al (2020) Co-morbidities and co-medications as confounders of cardioprotection—Does it matter in the clinical setting? Br J Pharmacol 177(23):5252–5269
doi: 10.1111/bph.14839
pubmed: 31430831
pmcid: 7680006
Schulz R et al (2020) Risk factors, co-morbidities, and co-medications in cardioprotection: Importance for translation. Br J Pharmacol 177(23):5249
doi: 10.1111/bph.15294
pubmed: 33219717
pmcid: 7679999
Ruiz-Meana M et al (2020) Ageing, sex, and cardioprotection. Br J Pharmacol 177(23):5270–5286
doi: 10.1111/bph.14951
pubmed: 31863453
pmcid: 7680010
Andreadou I et al (2020) The role of mitochondrial reactive oxygen species, NO and H2S in ischaemia/reperfusion injury and cardioprotection. J Cell Mol Med 24(12):6510–6522
doi: 10.1111/jcmm.15279
pubmed: 32383522
pmcid: 7299678
Picca A et al (2018) Mitochondrial quality control mechanisms as molecular targets in cardiac ageing. Nat Rev Cardiol 15(9):543–554
doi: 10.1038/s41569-018-0059-z
pubmed: 30042431
pmcid: 6283278
Marin W et al (2021) Mitochondria as a therapeutic target for cardiac ischemia-reperfusion injury. Int J Mol Med 47(2):485–499
doi: 10.3892/ijmm.2020.4823
pubmed: 33416090
Zhou H et al (2021) Role of mitochondrial quality surveillance in myocardial infarction: from bench to bedside. Ageing Res Rev 66:101250
doi: 10.1016/j.arr.2020.101250
pubmed: 33388396
Algoet, M., et al., ‘Myocardial ischemia-reperfusion injury and the influence of inflammation. Trends in Cardiovascular Medicine, 2022.
Huang, J., R. Li, and C. Wang, The role of mitochondrial quality control in cardiac ischemia/reperfusion injury. Oxidative Medicine and Cellular Longevity, 2021.
Zhou M et al (2021) Myocardial Ischemia-Reperfusion Injury: Therapeutics from a Mitochondria-Centric Perspective. Cardiology 146(6):781–792
doi: 10.1159/000518879
pubmed: 34547747
Nejati K et al (2020) GDNF gene-engineered adipose-derived stem cells seeded Emu oil-loaded electrospun nanofibers for axonal regeneration following spinal cord injury. Journal of Drug Delivery Science and Technology 60:102095
doi: 10.1016/j.jddst.2020.102095
Mokhtari B et al (2020) Comparison of the effects of intramyocardial and intravenous injections of human mesenchymal stem cells on cardiac regeneration after heart failure. Iran J Basic Med Sci 23(7):879
pubmed: 32774809
pmcid: 7395194
Alijani-Ghazyani Z et al (2021) Conditioned medium harvested from Hif1α engineered mesenchymal stem cells ameliorates LAD-occlusion-induced injury in rat acute myocardial ischemia model. Int J Biochem Cell Biol 130:105897
doi: 10.1016/j.biocel.2020.105897
pubmed: 33279679
Sagaradze G et al (2019) Conditioned medium from human mesenchymal stromal cells: towards the clinical translation. Int J Mol Sci 20(7):1656
doi: 10.3390/ijms20071656
pubmed: 30987106
pmcid: 6479925
Mokhtari B, Badalzadeh R, Aboutaleb N (2021) Modulation of autophagy as the target of mesenchymal stem cells-derived conditioned medium in rat model of myocardial ischemia/reperfusion injury. Mol Biol Rep 48(4):3337–3348
doi: 10.1007/s11033-021-06359-0
pubmed: 33895973
Mokhtari B et al (2020) Human amniotic membrane mesenchymal stem cells-conditioned medium attenuates myocardial ischemia-reperfusion injury in rats by targeting oxidative stress. Iran J Basic Med Sci 23(11):1453
pubmed: 33235703
pmcid: 7671430
Xin C et al (2020) Irisin attenuates myocardial ischemia/reperfusion injury and improves mitochondrial function through AMPK pathway in diabetic mice. Front Pharmacol 11:565160
doi: 10.3389/fphar.2020.565160
pubmed: 33013403
pmcid: 7516196
Miwa S et al (2022) Mitochondrial dysfunction in cell senescence and aging. J Clin Investig 132(13):e158447
doi: 10.1172/JCI158447
pubmed: 35775483
pmcid: 9246372
Quan Y et al. (2020) Mitochondrial ROS-modulated mtDNA: a potential target for cardiac aging. Oxidative medicine and cellular longevity
Zia A et al (2022) The roles of mitochondrial dysfunction and reactive oxygen species in aging and senescence. Curr Mol Med 22(1):37–49
doi: 10.2174/1566524021666210218112616
pubmed: 33602082
García-Niño WR et al (2021) Mitochondrial Quality Control in Cardiac-Conditioning Strategies against Ischemia-Reperfusion Injury. Life 11(11):1123
doi: 10.3390/life11111123
pubmed: 34832998
pmcid: 8620839
Anzell AR et al (2018) Mitochondrial quality control and disease: insights into ischemia-reperfusion injury. Mol Neurobiol 55(3):2547–2564
doi: 10.1007/s12035-017-0503-9
pubmed: 28401475
Svaguša T et al (2020) Mitochondrial unfolded protein response, mitophagy and other mitochondrial quality control mechanisms in heart disease and aged heart. Croat Med J 61(3):126–138
doi: 10.3325/cmj.2020.61.126
pubmed: 32378379
pmcid: 7230417
Ghasemi A, Jeddi S, Kashfi K (2021) The laboratory rat: Age and body weight matter. EXCLI J 20:1431
pubmed: 34737685
pmcid: 8564917
Yang, M., et al., Mitophagy and mitochondrial integrity in cardiac ischemia-reperfusion injury. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2019. 1865(9): p. 2293–2302.
Oh C-M et al (2020) Mitochondrial quality control in the heart: new drug targets for cardiovascular disease. Korean Circulation Journal 50(5):395–405
doi: 10.4070/kcj.2019.0416
pubmed: 32216174
pmcid: 7098821
Yamaguchi S et al (2015) Dental pulp-derived stem cell conditioned medium reduces cardiac injury following ischemia-reperfusion. Sci Rep 5(1):1–10
doi: 10.1038/srep16295
Danieli P et al (2015) Conditioned medium from human amniotic mesenchymal stromal cells limits infarct size and enhances angiogenesis. Stem Cells Transl Med 4(5):448–458
doi: 10.5966/sctm.2014-0253
pubmed: 25824141
pmcid: 4414224
Timmers L et al (2008) Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium. Stem cell research 1(2):129–137
doi: 10.1016/j.scr.2008.02.002
Timmers L et al (2011) Human mesenchymal stem cell-conditioned medium improves cardiac function following myocardial infarction. Stem cell research 6(3):206–214
doi: 10.1016/j.scr.2011.01.001
pubmed: 21419744