title: A DPP-4 inhibitor suppresses fibrosis and inflammation on experimental autoimmune myocarditis in mice.
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.
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hirakawa
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Zempo
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Watanabe
authors.affiliation: Department of Advanced Clinical Science and Therapeutics, The University of Tokyo, Tokyo, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Suzuki
authors.affiliation: Department of Advanced Clinical Science and Therapeutics, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akazawa
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Isobe
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005355:Fibrosis; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006334:Heart Function Tests; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000069476:Linagliptin / Q000494:pharmacology* / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D000069476:Linagliptin