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:
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