A DPP-4 Inhibitor Suppresses Fibrosis and Inflammation on Experimental Autoimmune Myocarditis in Mice |
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| Authors: | Hiroyuki Hirakawa Hirofumi Zempo Masahito Ogawa Ryo Watanabe Jun-ichi Suzuki Hiroshi Akazawa Issei Komuro Mitsuaki Isobe |
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| Affiliation: | 1. Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.; 2. Department of Advanced Clinical Science and Therapeutics, The University of Tokyo, Tokyo, Japan.; 3. Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.; Osaka University Graduate School of Medicine, JAPAN, |
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| Abstract: | Myocarditis is a critical inflammatory disorder which causes life-threatening conditions. No specific or effective treatment has been established. DPP-4 inhibitors have salutary effects not only on type 2 diabetes but also on certain cardiovascular diseases. However, the role of a DPP-4 inhibitor on myocarditis has not been investigated. To clarify the effects of a DPP-4 inhibitor on myocarditis, we used an experimental autoimmune myocarditis (EAM) model in Balb/c mice. EAM mice were assigned to the following groups: EAM mice group treated with a DPP-4 inhibitor (linagliptin) (n = 19) and those untreated (n = 22). Pathological analysis revealed that the myocardial fibrosis area ratio in the treated group was significantly lower than in the untreated group. RT-PCR analysis demonstrated that the levels of mRNA expression of IL-2, TNF-α, IL-1β and IL-6 were significantly lower in the treated group than in the untreated group. Lymphocyte proliferation assay showed that treatment with the DPP-4 inhibitor had no effect on antigen-induced spleen cell proliferation. Administration of the DPP-4 inhibitor remarkably suppressed cardiac fibrosis and reduced inflammatory cytokine gene expression in EAM mice. Thus, the agents present in DPP-4 inhibitors may be useful to treat and/or prevent clinical myocarditis. |
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