Pharmacological Preconditioning of Mesenchymal Stem Cells with Trimetazidine (1-[2,3,4-Trimethoxybenzyl]piperazine) Protects Hypoxic Cells against Oxidative Stress and Enhances Recovery of Myocardial Function in Infarcted Heart through Bcl-2 Expression
| Autor: | Simi M. Chacko, Sheik Wisel, M. Lakshmi Kuppusamy, I. Krishna Mohan, Periannan Kuppusamy, Benjamin Sun, Kálmán Hideg, Mahmood Khan, Brian K. Rivera |
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| Rok vydání: | 2009 |
| Předmět: |
Cell Survival
Vasodilator Agents medicine.medical_treatment Blotting Western Myocardial Infarction Trimetazidine Pharmacology Biology Cardiovascular Mesenchymal Stem Cell Transplantation medicine.disease_cause Oxygen Consumption medicine Animals Cyclin D1 Myocardial infarction Reverse Transcriptase Polymerase Chain Reaction Mesenchymal stem cell Mesenchymal Stem Cells Stem-cell therapy Hypoxia (medical) medicine.disease Cell Hypoxia Rats Inbred F344 Rats Transplantation Disease Models Animal Oxidative Stress Immunology Molecular Medicine Stem cell medicine.symptom Oxidative stress medicine.drug |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 329:543-550 |
| ISSN: | 1521-0103 0022-3565 |
| Popis: | Stem cell transplantation is a possible therapeutic option to repair ischemic damage to the heart. However, it is faced with a number of challenges including the survival of the transplanted cells in the ischemic region. The present study was designed to use stem cells preconditioned with trimetazidine (1-[2,3,4-trimethoxybenzyl]piperazine; TMZ), a widely used anti-ischemic drug for treating angina in cardiac patients, to increase the rate of their survival after transplantation. Bone marrow-derived rat mesenchymal stem cells (MSCs) were subjected to a simulated host tissue environment by culturing them under hypoxia (2% O(2)) and using hydrogen peroxide (H(2)O(2)) to induce oxidative stress. MSCs were preconditioned with 10 microM TMZ for 6 h followed by treatment with 100 microM H(2)O(2) for 1 h and characterized for their cellular viability and metabolic activity. The preconditioned cells showed a significant protection against H(2)O(2)-induced loss of cellular viability, membrane damage, and oxygen metabolism accompanied by a significant increase in HIF-1alpha, survivin, phosphorylated Akt (pAkt), and Bcl-2 protein levels and Bcl-2 gene expression. The therapeutic efficacy of the TMZ-preconditioned MSCs was evaluated in an in vivo rat model of myocardial infarction induced by permanent ligation of left anterior descending coronary artery. A significant increase in the recovery of myocardial function and up-regulation of pAkt and Bcl-2 levels were observed in hearts transplanted with TMZ-preconditioned cells. This study clearly demonstrated the potential benefits of pharmacological preconditioning of MSCs with TMZ for stem cell therapy for repairing myocardial ischemic damage. |
| Databáze: | OpenAIRE |
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