Linagliptin, A Xanthine-Based Dipeptidyl Peptidase-4 Inhibitor, Ameliorates Experimental Autoimmune Myocarditis

This study sought to show the mechanism of how to ameliorate experimental autoimmune myocarditis (EAM) by administering dipeptidyl peptidase (DPP)-4 inhibitor linagliptin. The number of RAR-related orphan nuclear receptor gamma–positive Th17 cells infiltrated to the EAM myocardium was significantly...

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Detalles Bibliográficos
Autores principales: Shiheido-Watanabe, Yuka, Maejima, Yasuhiro, Kasama, Takeshi, Tamura, Natsuko, Nakagama, Shun, Ito, Yusuke, Hirao, Kenzo, Isobe, Mitsuaki, Sasano, Tetsuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Preclinical Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246030/
https://www.ncbi.nlm.nih.gov/pubmed/34222724
http://dx.doi.org/10.1016/j.jacbts.2021.04.006
Descripción
Sumario:This study sought to show the mechanism of how to ameliorate experimental autoimmune myocarditis (EAM) by administering dipeptidyl peptidase (DPP)-4 inhibitor linagliptin. The number of RAR-related orphan nuclear receptor gamma–positive Th17 cells infiltrated to the EAM myocardium was significantly attenuated by linagliptin treatment. Tandem mass spectrometry–based analysis demonstrated that DPP-4 binds to cathepsin G in EAM hearts, thereby protecting cathepsin G activity through inhibiting SerpinA3N activity. Linagliptin suppresses oxidative stress in EAM hearts as well. Thus, we found that DPP-4 plays a detrimental role in the progression of EAM by interacting with cathepsin G, which, in turn, suppresses SerpinA3N activity.

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