Abstract 1282: Interleukin-11 Prevents Cardiac Remodeling after Myocardial Infarction with Neovascularization in Murine Model.
Background: Cardiac remodeling after myocardial infarction (MI) results in ischemic cardiomyopathy, one of major causes of heart failure. Cardiac remodeling is positively or negatively modified by various kinds of neurohumoral factors. Among them, interleukin (IL)-6 family cytokines play important roles in cytoprotection and angiogenesis in response to cardiac stresses; however, their clinical application has not been proposed because most of them have proinflammatory properties. In spite of this limitation, IL-11, a pleiotropic member of the IL-6 cytokine family, is clinically available in the treatment of chemotherapy-induced thrombocytopenia without severe inflammatory reactions. Thus, we examined the effects of IL-11 on post-infarct cardiac remodeling, in order to address the possibility of clinical application of IL-11 as anti-heart failure therapy.
Methods and Results: Immunoblot analyses revealed that stimulation with IL-11 rapidly phosphorylated STAT3 in cultured rat cardiomyocytes. Similarly, intravenous administration of IL-11 (8 μg/kg) in C57Bl/6 mice resulted in the phosphorylation of STAT3 with a peak at 15 min, analyzed by immunoblotting. Concomitantly, immunofluoresence microscopic analyses demonstrated that STAT3 was translocated into nuclei of cardiac myocytes in response to IL-11 injection in vivo. In order to investigate the effects of IL-11 on cardiac remodeling after MI, C57Bl/6 mice were exposed to MI and IL-11 was intravenously injected from 24 h after MI for 5 days consecutively. Masson trichrome staining showed that IL-11 treatment induced attenuation of infarct size 2 weeks after MI (31.3 ± 1.7% in IL-11 treatment group versus 42.6 ± 4.6% in control, P<0.05). In border region, immunohistochemical examination using anti-CD31 antibody demonstrated that the number of vessels was increased to 1.2 fold in the IL-11 treatment group, compared with control group. Furthermore, vascular endothelial growth factor (VEGF) mRNA was increased 1.7 ± 0.1 fold (P<0.05, n=3) in normal murine hearts at 8 h after IL-11 administration.
Conclusions: The treatment with IL-11 prevents cardiac remodeling after MI accompanied with neovascularization. IL-11 treatment could be a promising strategy against heart failure.