Abstract 15969: Aav9-wnt11 Gene Therapy Improves Survival of Myocarditis Mice Induced by Coxsackie Virus Through the Improvement of Cardiac Function
Background: The wnt signaling pathway plays important roles in development and diseases. Recent reports suggest a relationship between the noncanonical Wnt signaling and the regulation of inflammation in various pathogenic disorders.
Objective: To investigate the effect of myocardial Wnt11 gene therapy on myocarditis model by coxsackie virus B3.
Methods: The effect of Wnt11 gene therapy on coxackievirus B3-induced myocarditis model was examined using male BALB/c mice. Mice received single intravenous injection of either AAV9-Wnt11 or control virus (AAV9-LacZ) two weeks before administration of coxsackievirus B3 injected intraperitoneally. Transgene expression and tissue distribution were assessed at multiple time points by RNA and protein analysis. Cardiac function was evaluated by echocardiography at days 4 and 7 after administration of coxsackievirus B3. RNA expression of inflammatory cytokines was examined by quantitative RT-PCR.
Results: Intravenous injection of AAV9-Wnt11 resulted in efficient, durable, and relatively cardiac-specific Wnt11 expression. Survival was significantly greater among Wnt11-treated mice than among control-treated mice (87.5% Wnt 11 vs 58.2% control, p<0.05), and Wnt11-treated mice also showed significantly a greater cardiac ejection fraction compared to control mice(77.5% Wnt 11 vs 62.9% control, p<0.05). RNA expression of inflammatory cytokines such as Interleukin(IL)-6 and IL-1beta was significantly suppressed in Wnt11-treated mice.
Conclusions: This is the firstreport to show Wnt11 improves survival of coxsackievirus B3-induced myocarditis mice.
AAV9-mediated Wnt11 gene therapy produces beneficial effects on cardiacfunction and survival of mice with coxsackievirus B3-induced myocarditis through the suppression of inflammatory cytokines gene expression.
- © 2012 by American Heart Association, Inc.