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Conditioned Medium Reduces Isoproterenol-Induced Myocardial Damage Via MAPK/NF-κB Pathway

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Abstract

The present work was conducted to examine the cardioprotective effects of conditioned medium (CM) obtained from human amniotic membrane mesenchymal stem cells (hAMSCs-CM) in a rat model of isoproterenol (ISO)-induced myocardial damage and to clarify its effect on activity of mitogen-activated protein kinase (MAPK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. ISO was subcutaneously injected at 170 mg/kg/day for 4 consecutive days to create model. The cardiac function was determined using echocardiography. The expression of inflammatory cytokine was investigated using enzyme-linked immunosorbent assay (ELISA). The activity of MAPK/NF-κB was evaluated by immunohistochemistry assay. Trichrome Masson’s staining was used to evaluate the fibrosis. ISO-induced myocardial damage was indicated by loss of cardiac function, excessive secretion of inflammatory cytokines, increased fibrosis and activity of NF-κB and increasing phosphorylated levels of p38 MAPK. Intramyocardial post-treatment with 150 µL of hAMSCs-CM significantly improved heart function and reduced fibrosis and expression levels of inflammatory cytokines, NF-κB expression, and phosphorylated levels of p38 MAPK (p < 0. 05). Collectively, findings of present study demonstrate that cardioprotective effects of hAMSCs-CM are associated with attenuation of inflammation through reduction in activity of MAPK/NF-κB pathway. This can be attributed to paracrine factors secreted by MSCs including exosomes, cytokines, antiapoptotic, angiogenic, and growth factors.

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Acknowledgements

The research and publication of this article were supported by physiology research center of Iran University of Medical Sciences.

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Authors and Affiliations

  1. Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Maryam Naseroleslami

  2. Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran

    Nahid Aboutaleb

  3. Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Nahid Aboutaleb

Authors
  1. Maryam Naseroleslami
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  2. Nahid Aboutaleb
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Contributions

N.A participated in the design and interpretation of the study, data analysis, and the review of the manuscript. M.N conducted the experiment and collected the tissue and was responsible for the data analysis. N.A performed histopathological and immunochemical analyses. N.A and M.N wrote the manuscript, and all authors reviewed, read, and approved the article.

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Correspondence to Maryam Naseroleslami or Nahid Aboutaleb.

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Naseroleslami, M., Aboutaleb, N. Conditioned Medium Reduces Isoproterenol-Induced Myocardial Damage Via MAPK/NF-κB Pathway. Iran J Sci 47, 1115–1124 (2023). https://doi.org/10.1007/s40995-023-01504-9

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  • DOI: https://doi.org/10.1007/s40995-023-01504-9

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