Di-san junyi daxue xuebao (Jul 2019)
Intravenous delivery of a microRNA-1 agomir improves isoproterenol-induced heart failure in mice
Abstract
Objective To investigate the therapeutic effect of intravenous administration of a microRNA-1 (miR-1) agomir on isoproterenol (ISO)-induced heart failure (HF) in mice. Methods Mouse models of HF were established by intraperitoneal injection of ISO for 28 consecutive days at a daily dose of 60 mg/kg, and the control mice were injected with normal saline in the same manner. The success of modeling was verified by echocardiography on the next day after completion of the injections. On days 1 and 4 after successful modeling, the mice were received injections of a miR-1 agomir (miR-1 group) or a control agomir (model group) via the tail vein; the control mice were injected with normal saline only. The 3 groups of mice were again subjected to echocardiography on day 7. At the end of the experiment, the mice were sacrificed for assessing ventricular remodeling using HE staining, Sirius Red staining, WGA staining and Ki67 assay; the levels of serum NT-proBNP were detected using enzyme-linked immunosorbent assay, and the expression of mitochondrial calcium uniporter (MCU, the target gene of miR-1) in the cardiac tissues was detected with Western blotting and immunohistochemical staining. Results The HF model was successfully established by intraperitoneal injections of ISO for 28 consecutive days. Intravenous administration of the miR-1 agomir significantly improved cardiac function and ventricular remodeling. Compared with that in the model group, the serum level of NT-proBNP in the HF models was significantly lowered following treatment with the miR-1 agomir, but still remained higher than that in the control group (P < 0.05). The results of Western blotting and immunohistochemistry demonstrated a significant reduction of the expression of MCU in the cardiac tissues of miR-1-treated mice (P < 0.05). Conclusion Intravenous injection of the miR-1 agomir can improve ISO-induced HF in mice probably by modulating MCU expression in the cardiac tissues.
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