Bone marrow mesenchymal stromal cells rescue cardiac function in streptozotocin-induced diabetic rats
Autor: | Deivid C. Rodrigues, José Nascimento, Marcela S. Carneiro-Ramos, Barbara Guerra, M. C. Cabral-da-Silva, Danielle Carvalho Oliveira Coutinho, Gabriel Manso, Emiliano Medei, Mayra Trentin-Sonoda, Andrea Claudia Freitas Ferreira, Gustavo Monnerat-Cahli, Antonio Carlos Carvalho, Regina Coeli dos Santos Goldenberg, Diorney Luiz Souza Gran da Silva |
---|---|
Rok vydání: | 2014 |
Předmět: |
Blood Glucose
Male Cardiac function curve medicine.medical_specialty Heart Diseases medicine.medical_treatment Mesenchymal Stem Cell Transplantation Diabetes Mellitus Experimental Diabetes Complications Heart Conduction System Internal medicine Diabetes mellitus medicine Animals Rats Wistar Ventricular Remodeling business.industry Insulin Leptin Mesenchymal stem cell AMPK Mesenchymal Stem Cells Streptozotocin medicine.disease Rats Endocrinology medicine.anatomical_structure Hyperglycemia Bone marrow Corticosterone Cardiology and Cardiovascular Medicine business Biomarkers Signal Transduction medicine.drug |
Zdroj: | ResearcherID |
ISSN: | 0167-5273 |
DOI: | 10.1016/j.ijcard.2013.12.013 |
Popis: | Objectives In the present study, we investigated whether MSC-transplantation can revert cardiac dysfunction in streptozotocin-induced diabetic rats and the immunoregulatory effects of MSC were examined. Background Cardiac complications are one of the main causes of death in diabetes. Several studies have shown anti-diabetic effects of bone marrow mesenchymal stromal cells (MSC). Methods/results The rats were divided in three groups: Non-diabetic, Diabetic and Diabetic-Treated with 5×10 6 MSC 4weeks after establishment of diabetes. Four weeks after MSC-therapy, systemic metabolic parameters, immunological profile and cardiac function were assessed. MSC-transplantation was able to revert the hyperglycemia and body weight loss of the animals. In addition, after MSC-transplantation a decrease in corticosterone and IFN-γ sera levels without restoration of insulin and leptin plasma levels was observed. Also, MSC-therapy improved electrical remodeling, shortening QT and QTc in the ECG and action potential duration of left ventricular myocytes. No arrhythmic events were observed after MSC-transplantation. MSC-therapy rescued the cardiac beta-adrenergic sensitivity by increasing beta-1 adrenergic receptor expression. Both alpha and beta cardiac AMPK and p-AMPK returned to baseline values after MSC-therapy. However, total ERK1 and p-ERK1/2 were not different among groups. Conclusion The results indicate that MSC-therapy was able to rescue cardiac impairment induced by diabetes, normalize cardiac AMPK subunit expression and activity, decrease corticosterone and glycemia and exert systemic immunoregulation. |
Databáze: | OpenAIRE |
Externí odkaz: |