Novel Mesenchymal Stem Cell Strategy in Alleviating Toll-Like Receptor-4, p53 and Nrf2 Signaling in Isoproterenol-Induced Myocardial Infarction in Rat Model

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Abstract

Mesenchymal stem cells (MSCs) are multipotent stromal cells that merit the differentiation into various cell types. The present study was designed to test the hypothesis that the cardioprotective effect of MSCs transplantation and digoxin treatment is mediated via the regulation of messenger RNA gene expression of pro-inflammatory cytokines and apoptotic markers. Myocardial infarction was induced in Wistar rats via isoproterenol injection in a dose of (85 mg/kg, subcutaneously, twice at an interval of 24 h). Four weeks post-MSCs transplantation and digoxin treatment a significant reduction in serum cardiac markers, aspartate aminotransferase, creatine kinase-MB and troponine II was observed. Meanwhile, isoproterenol significantly reduced the gene and protein expression of the oxidative stress marker nuclear-related factor-2 (Nrf2) with a concomitant elevation in (MDA) level and inflammatory markers toll-like receptor-4 (TLR-4), intercellular adhesion molecules (ICAMs) and (VCAM-1). Moreover, apoptotic marker (P53) was significantly down-regulated. This was confirmed by histopathological investigations. It was hypothesized that MSCs transplantation was superior over digoxin treatment regimen in improving heart function.

Keywords

Myocardial infarction Mesenchymal stem cells Toll-like receptor-4 P53 

Notes

Acknowledgement

The authors thank Prof. Dr. Laila Rashed, Professor of Biochemistry, Faculty of Medicine, Cairo University for technical aid and Prof. Dr. Olfat Ali Hammam, Professor of Pathology Theodor Bilharz Research Institute for histopathological aid.

Compliance with Ethical Standards

Conflict of interest

The authors have no conflicts of interest to declare.

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© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Biochemistry, Therapeutic Chemistry DepartmentNational Research CenterGizaEgypt
  2. 2.Molecular Biology, Therapeutic Chemistry DepartmentNational Research CenterGizaEgypt

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