1. Mesenchymal stem cells improve cardiac function in diabetic rats by reducing cardiac injury biomarkers and downregulating JAK/STAT/iNOS and iNOS/Apoptosis signaling pathways.
- Author
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A-Elgadir TME, Shati AA, Alqahtani SA, Ebrahim HA, Almohaimeed HM, ShamsEldeeen AM, Haidara MA, Kamar SS, Dawood AF, and El-Bidawy MH
- Subjects
- Animals, Male, Rats, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 metabolism, Down-Regulation, Heart Injuries metabolism, Heart Injuries etiology, Janus Kinase 2 metabolism, Janus Kinases metabolism, Nitric Oxide Synthase Type II metabolism, Rats, Wistar, STAT Transcription Factors metabolism, STAT3 Transcription Factor metabolism, Apoptosis drug effects, Biomarkers metabolism, Diabetes Mellitus, Experimental complications, Mesenchymal Stem Cell Transplantation methods, Mesenchymal Stem Cells metabolism, Signal Transduction
- Abstract
Cardiovascular complications are prevalent manifestations of type 2 diabetes mellitus (T2DM) and are usually the main cause of death. This study aims to show the underlying mechanisms of the potential therapeutic effect of mesenchymal stem cells (MSCs) on diabetic cardiac dysfunction. Twenty-four male Wistar rats were randomly assigned to one of three groups The control group received standard laboratory chow, and the groups with T2DM received a single dose of 45 mg/kg body weight of streptozotocin (STZ) after 3 weeks of pretreatment with a high-fat diet (HFD). Eight weeks after the diagnosis of T2DM, rats were divided into two groups: the T2DM model group and the T2DM + MSCs group. BM-MSCs were administered systemically at 2 × 10
6 cells/rat doses. A Significant amelioration in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and dyslipidemia was noted 2 weeks post-administration of MSCs. Administration of MSCs improved dyslipidemia, the altered cardiac injury biomarkers (p ≤ 0.0001), downregulated Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)/inducible Nitric oxide synthase (iNOS) and iNOS/Apoptosis signaling pathways. This was associated with improved cardiac dysfunction (impaired left ventricular performance and decreased contractility index). Our results show that MSCs ameliorate cardiac dysfunction associated with diabetic cardiomyopathy by lowering dyslipidemia and insulin resistance, inhibiting oxidative stress, and inflammation, downregulating JAK2/STAT3/iNOS and iNOS/Apoptosis signaling pathways., Competing Interests: Declaration of competing interest I declare that I have no conflicts of interest relevant to this work." The authors declare that they have no financial or non-financial conflicts of interest related to this research." The authors report no conflicts of interest in this work. The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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