Let-7g is involved in doxorubicin induced myocardial injury

Objectives: To investigate whether let-7g (miRNA) was involved in doxorubicin-induced cardiotoxicity. Methods: Rats were treated with doxorubicin at increasing doses (0 mg/kg, 6 mg/kg, 12 mg/kg, 18 mg/kg). Heart rate, pulse pressure and plasma cardiac troponin T concentrations were measured. Primary cultured myocardial cells were incubated with DOX at increasing concentrations (0 mu mol/1, 0.004 mu mol/1, 0.02 mu mol/1, 0.1 mu mol/1, 0.5 mu mol/1) for 24h. Cellular viability and the beat frequency were measured. For both rats and cultured cells, miRNA content was measured by real-time reverse-transcription PCR. Results: All DOX-treated rats had a decrease in heart rate, an increase in pulse pressure compared with control group after injections (p < 0.05). Concentration of cTnT was increased significantly in 18 mg/kg group. Content of let-7g decreased significantly (p < 0.05) in 18 mg/kg group in vivo and all the doxorubicin treated group in vitro. Conclusions: The down regulation of let-7g in the myocardial-injury model suggests that let-7g may play an important role in the development of cardiac disease. (C) 2012 Published by Elsevier B.V.