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Published on: June 3, 2018
A DPP-4 inhibitor suppresses fibrosis and inflammation on experimental autoimmune myocarditis in mice
Hiroyuki Hirakawa1, Hirofumi Zempo1, Masahito Ogawa1
1Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Insights
Dipeptidyl peptidase-4 (DPP-4) inhibitors reduced cardiac fibrosis and inflammatory gene expression in experimental autoimmune myocarditis (EAM) mice. These findings suggest DPP-4 inhibitors may offer a novel therapeutic strategy for myocarditis treatment.
Area of Science:
- Cardiovascular Research
- Immunology
- Pharmacology
Background:
- Myocarditis is a severe inflammatory heart condition with no established effective treatments.
- Dipeptidyl peptidase-4 (DPP-4) inhibitors are known for benefits in type 2 diabetes and some cardiovascular diseases.
- The potential therapeutic role of DPP-4 inhibitors in myocarditis remains unexplored.
Purpose of the Study:
- To investigate the effects of a DPP-4 inhibitor, linagliptin, on experimental autoimmune myocarditis (EAM) in a mouse model.
- To assess the impact of linagliptin on myocardial fibrosis and inflammatory markers in EAM.
- To determine if DPP-4 inhibition influences antigen-induced immune cell proliferation in the context of myocarditis.
Main Methods:
- An experimental autoimmune myocarditis (EAM) mouse model was utilized.
- EAM mice were divided into two groups: one treated with linagliptin and an untreated control group.
- Myocardial fibrosis was evaluated via pathological analysis, and inflammatory gene expression (IL-2, TNF-α, IL-1β, IL-6) was quantified using RT-PCR. Lymphocyte proliferation was assessed.
Main Results:
- Linagliptin treatment significantly reduced the myocardial fibrosis area in EAM mice compared to controls.
- mRNA expression levels of key inflammatory cytokines (IL-2, TNF-α, IL-1β, IL-6) were significantly lower in the linagliptin-treated group.
- DPP-4 inhibitor administration did not affect antigen-induced spleen cell proliferation.
Conclusions:
- Administration of the DPP-4 inhibitor linagliptin effectively suppressed cardiac fibrosis in the EAM model.
- Linagliptin significantly reduced the expression of inflammatory cytokine genes in the heart during experimental myocarditis.
- These findings indicate that DPP-4 inhibitors possess therapeutic potential for treating and/or preventing clinical myocarditis.
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.
